Nelson Pediatrics Review(MCQs)19ed_Complete

Nelson Pediatrics Review(MCQs)19ed 1. Which of the following statements regarding foster care is true? □A permanency plan must be made for a child in foster care no later than 12 mo from the child's entry into care □A mi ...

Nelson Pediatrics Review(MCQs)19ed 1. Which of the following statements regarding foster care is true? □A permanency plan must be made for a child in foster care no later than 12 mo from the child's entry into care □A minority of children in foster care have a history of abuse or neglect □The mission of foster care is to safely care for children while providing services to families to promote reunification □Most (>70%) of children in foster care are reunited with their families ■A and C description The mission of foster care is to provide for the health, safety, and well-being of children while assisting their families with services to promote reunification. Children entering foster care have frequently experienced early childhood trauma. More than 70% have a history of abuse, neglect, or both. Only about 50% of children achieve reunification. In the USA, the Adoption and Safe Families Act (P.L. 105-89) passed in 1997 requires that a permanency plan be made for each child no later than 12 mo after entry to foster care and that a petition to terminate parental rights typically must be filed when a child has been in foster care for at least 15 of the previous 22 mo. (See Chapter 35, page 134, and e35-1.) 2. A 4 yr old girl is admitted to the hospital for her third evaluation for vaginal bleeding. The mother noted bright red blood on the child's underwear. Previous examinations revealed a normal 4 yr old girl, Tanner stage 1, with normal external genitalia. Pelvic ultrasound results were normal, as was the serum estradiol level. The hemoglobin and platelet counts were normal, as were the bleeding time and coagulation studies. Findings on pelvic examination conducted under anesthesia also were normal. The next step in the examination is to: ■Determine the blood type of the blood on the underwear □Interrogate the father □Isolate the parents and child □Determine von Willebrand factor levels□Measure fibronectin in the vagina description Consideration of factitious disorder by proxy should be triggered when the reported symptoms are repeatedly noted by only one parent, appropriate testing fails to confirm a diagnosis, and seemingly appropriate treatment is ineffective. At times, the child's symptoms, their course, or the response to treatment may be incompatible with any recognized disease. Preverbal children are usually involved. Bleeding is a particularly common presentation. This may be caused by adding dyes to samples, adding blood (e.g., from the mother) to the child's sample, or giving the child an anticoagulant (e.g., warfarin). (See Chapter 37, page 146.) 3. Munchausen syndrome by proxy is characterized by all of the following EXCEPT: □Mother who appears devoted and wins over members of care team □Multiple hospitalizations and investigations without diagnosis □Symptoms on history but not witnessed by medical team ■Symptoms occurring in presence of different caregivers (e.g., while mother is out of town) □Use of medications or toxins description Symptoms in young children are mostly associated with proximity of the offending caregiver to the child. The mother may present as a devoted or even model parent who forms close relationships with members of the health care team. While appearing very interested in her child's condition, she may be relatively distant emotionally. (See Chapter 37, page 146.) 4. Which statement is false? ■Malnutrition is the second leading cause of acquired immune deficiency worldwide behind HIV infection □Zinc is important in immune function and linear growth □Kwashiorkor and marasmus are rare in developed countries □The Western diet is associated with increased noncommunicable disease description The significant global burden of malnutrition and undernutrition is the leading worldwide cause of acquired immunodeficiency and the major underlying factor for morbidity and mortality globally for children <5 yr of age. Zinc is a micronutrient that supports multiple metabolic functions in the body, is essential for normal immune functioning, and is required to support linear growth; zinc deficiency is associated with impaired immune functioning and poor linear growth. In parallel to the risk for nutrient and energy deficiencies, issues relating to excesses pose important challenges because of their negative health effects, such as obesity or cardiovascular disease risk factors. The nutrition transition under way in thedeveloping world from traditional diets to the Western diet has been associated with increases in noncommunicable diseases, often coexisting with undernutrition and malnutrition, observed sometimes in the same communities or even the same families. (See e41-1.) 5. Components of energy expenditure in children include: □Thermal effect of food □Basal metabolic rate □Energy for physical activity □Energy to support growth ■All of the above description The 3 components of energy expenditure in adults are the basal metabolic rate, the thermal effect of food (energy required for digestion and absorption), and energy for physical activity. Additional energy intake and expenditure are required to support growth and development for children. (See e41-4.) 6. Which of the following clinical scenarios increases the risk of vitamin A deficiency? □Vegetarian diet □Chronic intestinal disorders □Zinc deficiency ■B and C □All of the above description Vitamin A is an essential micronutrient because it cannot be biogenerated de novo by animals. It must be obtained from plants in the form of provitamin-A carotenoids. In the USA, grains and vegetables supply approximately 55% and dairy and meat products supply approximately 30% of vitamin A intake from food. Vitamin A and the provitamins-A are fat soluble, and their absorption depends on the presence of adequate lipid and protein within the meal. Chronic intestinal disorders or lipid malabsorption syndromes can result in vitamin A deficiency. In developing countries, subclinical or clinical zinc deficiency can increase the risk of vitamin A deficiency. There is also some evidence of marginal zinc intakes in children in the USA. (See Chapter 45, page 188.) 7. Which statement about vitamin A toxicity is NOT true?□Excess vitamin A in utero can cause congenital malformations □It may present as pseudotumor cerebri ■An infant with a preference for carrots and butternut squash may develop toxicity □It may cause fissures at the corners of the mouth, pruritus, and alopecia □Symptoms subside rapidly after withdrawing the source of the vitamin description Excessive intake of carotenoids is not associated with toxicity but can cause yellow coloration of the skin that disappears when intake is reduced; this disorder (carotenemia) is especially likely to occur in children with liver disease, diabetes mellitus, or hypothyroidism and in those who do not have enzymes that metabolize carotenoids. (See Chapter 45, page 191.) 8. Which statement about vitamin E is false? □The most common form of vitamin E is tocopherol ■Premature infants given formula with a high content of polyunsaturated fatty acids and iron supplementation are protected from deficiency □Cholestatic liver disease increases the risk of deficiency □Premature infants with vitamin E deficiency develop hemolysis, thrombocytosis, and edema □Prolonged vitamin E deficiency causes a severe, progressive neurologic disorder description Premature infants are particularly susceptible to vitamin E deficiency because there is significant transfer of vitamin E during the last trimester of pregnancy. Vitamin E deficiency in premature infants causes thrombocytosis, edema, and hemolysis, potentially causing anemia. The risk of symptomatic vitamin E deficiency was increased by the use of formulas for premature infants that had a high content of polyunsaturated fatty acids (PUFAs). These formulas led to a high content of PUFAs in red blood cell membranes, making them more susceptible to oxidative stress, which could be ameliorated by vitamin E. Oxidative stress was augmented by aggressive use of iron supplementation; iron increases the production of oxygen radicals. The incidence of hemolysis due to vitamin E deficiency in premature infants decreased secondary to the use of formulas with a lower content of polyunsaturated fatty acids, less-aggressive use of iron, and provision of adequate vitamin E. (See e49-1.) 9. Manifestations of hyperkalemia include all of the following EXCEPT:□Paresthesias □Weakness □Paralysis □Wide QRS complex ■Tetany description The most important effects of hyperkalemia are due to the role of potassium in membrane polarization. The cardiac conduction system is usually the dominant concern. Changes in the electrocardiogram (ECG) begin with peaking of the T waves. This is followed, as the potassium level increases, by ST segment depression, an increased PR interval, flattening of the P wave, and widening of the QRS complex. This process can eventually progress to ventricular fibrillation. Asystole may also occur. Some patients have paresthesias, fasciculations, weakness, and even an ascending paralysis, but cardiac toxicity usually precedes these clinical symptoms, emphasizing the danger of assuming that an absence of symptoms implies an absence of danger. (See Chapter 52, page 221.) 10. Hyperkalemia may be associated with all of the following EXCEPT: □Succinylcholine use □Burns □Trauma □Chemotherapy ■Metabolic alkalosis □Digitalis toxicity □Uremia description Many causes of hyperkalemia result in metabolic acidosis; a metabolic acidosis worsens hyperkalemia through the transcellular shift of potassium out of cells. Renal insufficiency is a common cause of the combination of metabolic acidosis and hyperkalemia. This association is also seen in diseases associated with aldosterone insufficiency or aldosterone resistance. (See Chapter 52, page 221.) 11. The best method to reduce the potassium level during hyperkalemia, by reducing the body burden of potassium, is:□Sodium bicarbonate infusion □Glucose and insulin infusion □Calcium infusion □Albuterol aerosol ■Kayexalate enema description Treatment of hyperkalemia has 2 basic goals: (1) to stabilize the heart to prevent life-threatening arrhythmias and (2) to remove potassium from the body. The treatments that acutely prevent arrhythmias all have the advantage of working quickly (within minutes) but do not remove potassium from the body. Calcium stabilizes the cell membrane of heart cells, preventing arrhythmias. It is given intravenously over a few minutes, and its action is almost immediate. Several medications cause potassium to move intracellularly and thus rapidly reduce the plasma level to prevent arrhythmias. These include bicarbonate, insulin and glucose, and nebulized albuterol. However, these medicines do not remove potassium from the body. To reduce the total body potassium, 3 options are available. In patients who are not anuric, a loop diuretic increases renal excretion of potassium. A high dose may be required in a patient with significant renal insufficiency. Sodium polystyrene sulfonate (Kayexalate) is an exchange resin that is given either rectally or orally. Sodium in the resin is exchanged for body potassium, and the potassium-containing resin is then excreted from the body. Some patients require dialysis for acute removal of potassium. Dialysis is often necessary if the patient has either severe renal failure or an especially high rate of endogenous potassium release, as is sometimes present with tumor lysis syndrome or rhabdomyolysis. (See Chapter 52, page 222.) 12. Clinical manifestations of hypokalemia include all of the following EXCEPT: □ECG changes □Paralysis □Urinary retention □Constipation □Muscle cramps ■Blurry vision description The heart and skeletal muscle are especially vulnerable to hypokalemia. ECG changes include a flattened T wave, a depressed ST segment, and the appearance of a U wave, which is located between the T wave (if still visible) and the P wave. Ventricular fibrillation and torsades de pointes may occur, although usually only in the context of underlying heart disease. The clinical consequences of hypokalemia in skeletal muscle include muscle weakness and cramps. Paralysis is a possible complication, generally only at potassium levels <2.5 mEq/L. It usually starts in the legs and moves to the arms. Respiratory paralysis may require mechanical ventilation. Some patients have rhabdomyolysis; the risk increases withexercise. Hypokalemia slows gastrointestinal motility. This effect manifests as constipation; with potassium levels <2.5 mEq/L, an ileus may occur. Hypokalemia impairs bladder function, potentially leading to urinary retention. (See Chapter 52, page 224.) 13. From the following list, choose the route(s) by which insensible water loss may occur: 1. Sweat, 2. Fecal loss, 3. Evaporative loss from skin, 4. Respiratory water loss, 5. Obligate water for urinary solute excretion □1 and 3 □1, 2, and 3 □3 only ■3 and 4 □2 and 5 description Water is a crucial component of maintenance fluid therapy because of the obligatory daily water losses. These losses are both measurable (urine, stool) and not measurable (insensible losses from the skin and lungs). Failure to replace these losses leads to a child who is thirsty, uncomfortable, and, ultimately, dehydrated. (See Chapter 53, page 242.) 14. Which of the following is a goal of maintenance fluids? □Diminish protein degradation □Prevent dehydration ■Prevent hunger □Prevent electrolyte derangements □Prevent ketoacidosis description The glucose in maintenance fluids provides approximately 20% of the normal caloric needs of the patient, prevents the development of starvation ketoacidosis, and diminishes the protein degradation that would occur if the patient received no calories. Glucose also provides added osmoles, thus avoiding the administration of hypotonic fluids that may cause hemolysis. Maintenance fluids do not provide adequate calories, protein, fat, minerals, or vitamins. This fact is typically not problematic for a patient receiving intravenous fluids for a few days. A patient receiving maintenance intravenous fluids is receiving inadequate calories and will lose 0.5-1% of weight each day. Table 53-1 summarizes the goals of maintenance fluids. (See Chapter 53, page 242.)15. Which patient has an elevated risk of hyponatremia with standard maintenance fluid therapy (D5 ½ NS if >10 kg, D5 ¼ NS if <10 kg)? □6 mo old NPO for elective hernia repair □4 month old with bronchiolitis and poor oral intake □13 yr old status post motor vehicle accident with multiple fractures, requiring treatment with narcotics and antiemetics □8 yr old with nephrotic syndrome □A and D ■B, C, and D description Patients who are producing antidiuretic hormone (ADH) may retain water, creating a risk of hyponatremia due to water intoxication. Patients who may be producing ADH owing to subtle volume depletion or other mechanisms (respiratory disease, stress, pain, nausea, medications such as narcotics) may be more safely treated with fluids that have a higher sodium concentration, with a decrease in fluid rate, or with a combination of these strategies. Patients with persistent ADH production due to an underlying disease process (syndrome of inappropriate ADH secretion [SIADH], congestive heart failure, nephrotic syndrome, liver disease) should receive less than maintenance fluids. Treatment is individualized, and careful monitoring is critical. Special caution is needed in patients who are known to have low-normal serum sodium concentrations or hyponatremia. (See Chapter 52, page 243.) 16. In which patient is oral rehydration NOT indicated? □2 yr old with moderate hypernatremic dehydration □6 mo old with mild hyponatremic dehydration ■4 mo old with severe dehydration and normal serum sodium □3 yr old with moderate dehydration and normal serum sodium □A and C description Dehydration, most often due to gastroenteritis, is a common problem in children. Most cases can be managed with oral rehydration. Even children with mild to moderate hyponatremic or hypernatremic dehydration can be managed with oral rehydration. The infant with severe dehydration is gravely ill. The decrease in blood pressure indicates that vital organs may be receiving inadequate perfusion. Immediate and aggressive intervention is necessary. If possible, the child with severe dehydration initially should receive intravenous therapy. (See Chapter 54, page 245.)17. Which statement about pediatric poisoning is NOT true? □Most poisonings among young children involve a single substance and are unintentional □Poison prevention should be discussed at all well child visits beginning at 6 months □Pediatric poisonings occur most frequently in the toddler and adolescent age ranges ■The toddler age group experiences the majority of poisoning deaths □Poison control centers are available via phone, 24-7, toll free description Although the majority of exposures are in children <6 yr, only 2% of the reported deaths occur in this age group. In addition to the exploratory nature of ingestions in young children, product safety measures, poison prevention education, early recognition of exposures, and around-the-clock access to regionally based poison control centers all contribute to the favorable outcomes in this age group. Exposures in the adolescent age group are primarily intentional (suicide or abuse or misuse of substances) and thus often result in more severe toxicity. Adolescents (ages 13-19 yr) accounted for 74 of the 108 poison-related pediatric deaths in 2008 reported to the National Poison Data System. Pediatricians should be aware of the signs of drug abuse or suicidal ideation in this population and should aggressively intervene. (See Chapter 58, page 250.) 18. Quantitative levels of certain medications are helpful in the management of acute poisonings. For which of the following medications is this NOT true? □Salicylates □Acetaminophen □Iron □Carbon monoxide ■Marijuana description For select intoxications (salicylates, some anticonvulsants, acetaminophen, iron, digoxin, methanol, lithium, theophylline, ethylene glycol, carbon monoxide), quantitative blood concentrations are integral to confirming the diagnosis and formulating a treatment plan. For most exposures, quantitative measurement is not readily available and is not likely to alter management. (See Chapter 58, page 253.) 19. The 4 principles of management of poisonings are what? ■Decontamination, enhanced elimination, antidote, supportive care□Degradation, hydration, oxygenation, antidote □Ipecac, clinical monitoring, dialysis, reversal □Alkalinization, oxygenation, elimination, hydration description The 4 principles of management of the poisoned patient are decontamination, enhanced elimination, antidote, and supportive care. Few patients meet criteria for all of these interventions, although clinicians should consider each option in every poisoned patient so as not to miss a potentially lifesaving therapy. Antidotes are available for relatively few poisons, thus emphasizing the importance of meticulous supportive care and close clinical monitoring. (See Chapter 58, page 254.) 20. A 15 yr old boy is admitted to your care after the intentional ingestion of 2 g of his own amitriptyline in a suicide gesture. He received activated charcoal for gastrointestinal decontamination. The patient is placed in the ICU for monitoring and remains stable. He is receiving only 0.45% normal saline. You observe a change in his cardiac monitor display with a widening of his QRS complex to 0.12 second and occasional ectopic beats. The most appropriate next step in management is to: □Ignore these changes because they are still within normal limits ■Add sodium bicarbonate to his IV fluids to try to raise his serum pH above 7.4 □Repeat a dose of activated charcoal □Begin a lidocaine infusion at an appropriate dose □Order a chest radiograph description Sodium bicarbonate is the antidote of choice for TCA toxicity and works via overcoming the sodium channel blockade by providing a sodium load and via inducing an alkalosis to decrease drug binding to sodium channels. Indications for sodium bicarbonate include a QRS duration >100 msec, ventricular dysrhythmias, and hypotension. An initial bolus of 1-2 mEq/kg of sodium bicarbonate is given followed by initiation of a continuous infusion. Additional boluses may be given if the QRS duration continues to widen, with the goals of therapy being a serum pH of 7.45-7.55, improved hemodynamic stability, and narrowing of the QRS complex. (See Chapter 58, page 264.) 21. A 2 yr old boy arrives in the emergency department after a seizure. On presentation his vital signs are: temperature 40.2°C, heart rate 200 beats/min, respiratory rate 52 breaths/min. His laboratory values are: arterial pH 7.2, serum bicarbonate 6 mmol/L, arterial PCO2 18 mm Hg, sodium 148 mmol/L, potassium 3.1 mmol/L, WBC count 10,200/mm3. On the basis of the history obtained and the presentation, you suspect that an accidental ingestion has occurred. The most likely toxin is: □A tricyclic antidepressant□Acetaminophen □Cocaine □An organophosphate insecticide ■A salicylate description Salicylate ingestions are classified as acute or chronic, and acute toxicity is far more common in pediatric patients. Early signs of acute salicylism include nausea, vomiting, diaphoresis, and tinnitus. Moderate salicylate toxicity can manifest as tachypnea and hyperpnea, tachycardia, and altered mental status. The tachycardia results in large part from marked insensible losses from vomiting, tachypnea, diaphoresis, and uncoupling of oxidative phosphorylation. Thus, careful attention should be paid to volume status and early volume resuscitation in the significantly poisoned patient. Signs of severe salicylate toxicity include hyperthermia, coma, and seizures. Chronic salicylism can have a more insidious presentation, and patients can show marked toxicity at significantly lower salicylate levels than in acute toxicity. The classic blood gas of salicylate toxicity reveals a primary respiratory alkalosis and a primary, anion gap, metabolic acidosis. Hyperglycemia (early) and hypoglycemia (late) have been described. Abnormal coagulation studies, clinically manifested as bleeding and easy bruising, also may be seen. (See Chapter 58, page 260.) 22. A 2 yr old boy is noted to be drinking from a container filled with kerosene. He immediately coughs, becomes tachypneic, and is brought to the hospital. The best approach to his treatment is to: □Induce emesis □Perform nasogastric tube lavage □Instill mineral oil □Administer steroids ■None of the above description The most important manifestation of hydrocarbon toxicity is aspiration pneumonitis. Aspiration usually occurs during coughing and gagging at the time of ingestion or vomiting after the ingestion. The propensity of a hydrocarbon to cause aspiration pneumonitis is inversely proportional to its viscosity. Compounds with low viscosity, such as mineral spirits, naphtha, kerosene, gasoline, and lamp oil, spread rapidly across surfaces and cover large areas of the lungs when aspirated. Only small quantities (<1 mL) of low-viscosity hydrocarbons need be aspirated to produce significant injury. Respiratory symptoms can remain mild or progress rapidly to acute respiratory distress syndrome (ARDS) and respiratory failure. Emesis and lavage are contraindicated given the risk of aspiration. Activated charcoal is not useful because it does not bind the common hydrocarbons and can also induce vomiting. If hydrocarbon-induced pneumonitis develops, respiratory treatment is supportive. Neither corticosteroids nor prophylactic antibiotics have shown any clear benefit. (See Chapter 58, page 267.)23. A 2 yr old child is found playing with a can of crystalline drain cleaner. The child's mother telephones you for help. There are several crystals in the mouth, which you have the mother wash out. The next step in treatment should be to: □Have the mother administer lemon juice or orange juice to neutralize the alkaline crystals and come to your office □Have the mother administer water or milk and call you back in 2 hr ■Have the mother administer water or milk and bring the child in for esophagoscopy □Simply observe the child because the crystals are so bitter that the child was trying to spit them out when the mother called, and therefore no problems should occur □Administer ipecac at home and bring the child in to see you description Alkalis produce a liquefaction necrosis, allowing further tissue penetration of the toxin and setting the stage for possible perforation. Ingestion of caustic materials can produce injury to the oral mucosa, esophagus, and stomach. Patients can have significant esophageal injury even in the absence of visible oral burns. Symptoms include pain, drooling, vomiting, abdominal pain, and difficulty swallowing or refusal to swallow. Laryngeal injury can manifest as stridor and respiratory distress, necessitating intubation. In the most severe cases, patients can present in shock after perforation of a hollow viscus. Initial treatment of caustic exposures includes thorough removal of the product from the skin or eye by flushing with water. Emesis and lavage are contraindicated. Activated charcoal should not be used because it does not bind these agents and can predispose the patient to vomiting and subsequent aspiration. Endoscopy should be performed within 12-24 hr of ingestion in symptomatic patients or those in whom injury is suspected on the basis of history and known characteristics of the ingested product. (See Chapter 58, page 266.) 24. A 16 yr old, 165-lb patient reports consuming 20-40 325-mg capsules containing acetaminophen 1 hr ago. The most appropriate approach to treatment is to: □Measure the plasma level and determine potential toxicity from the level on the nomogram □Wait until 4 hr after ingestion to measure the plasma level and do nothing else ■Administer activated charcoal immediately and measure the plasma level of acetaminophen 4 hr after ingestion □Send the patient home because an ingestion of this magnitude is not toxic □Administer N-acetylcysteine at a dose of 140 mg/kg description Initial treatment should focus on the ABCs and consideration of decontamination with activated charcoal in patients who present within 1-2 hr of ingestion. The antidote for acetaminophen poisoning is NAC, which works primarily via replenishing hepatic glutathione stores. NAC therapy is most effective when initiated within 8 hr of ingestion. However, there is no demonstrated benefit to giving NAC before the 4 hr postingestion mark. Thus, patients who present early after ingestion should have a 4-hr level drawn and decision to initiate NAC should be based on this level. (See Chapter 58, page259.) 25. A 2 yr old child presents in the emergency department after the reported ingestion of a mouthful of lamp oil. The child reportedly vomited once at home. The child has a heart rate of 160 beats/min, a respiratory rate of 48 breaths/min, and a temperature of 37.2°C. A chest film is read as normal. The most appropriate therapy for this child is to: □Administer syrup of ipecac □Administer activated charcoal □Remove any ingested lamp oil by gastric lavage ■Admit the child for observation and supportive care □Discharge the child home with a follow-up office visit in the morning description The most important manifestation of hydrocarbon toxicity is aspiration pneumonitis. Aspiration usually occurs during coughing and gagging at the time of ingestion or vomiting after the ingestion. The propensity of a hydrocarbon to cause aspiration pneumonitis is inversely proportional to its viscosity. Compounds with low viscosity, such as mineral spirits, naphtha, kerosene, gasoline, and lamp oil, spread rapidly across surfaces and cover large areas of the lungs when aspirated. Only small quantities (<1 mL) of low-viscosity hydrocarbons need be aspirated to produce significant injury. Chest radiographs may initially be normal, but they often show abnormalities within 6 hr of exposure in patients who have aspirated. Respiratory symptoms can remain mild or progress rapidly to acute respiratory distress syndrome (ARDS) and respiratory failure. Emesis and lavage are contraindicated given the risk of aspiration. Activated charcoal is not useful because it does not bind the common hydrocarbons and can also induce vomiting. If hydrocarbon-induced pneumonitis develops, respiratory treatment is supportive. (See Chapter 58, page 267.) 26. A teenage girl presents in the emergency department with the story that she got upset with her boyfriend and swallowed a "handful of aspirin" about 4 hr previously. One hour afterward, after she began vomiting, she confessed to her mother what she had done. On examination the patient has normal vital signs and is asymptomatic except for the complaint of nausea. A serum salicylate level is ordered, but the laboratory reports no salicylates in her blood. The most appropriate next step in management is to: □Discharge the patient home ■Order an acetaminophen level □Request a psychiatric consultation □Send a second sample for salicylate determination□Order an abdominal radiograph to look for pills in the stomach description Acetaminophen is a widely available medication and a commonly detected co-ingestant with the potential for severe toxicity. Given that patients might initially be asymptomatic and might not report acetaminophen as a co-ingestant, an acetaminophen level should be checked in all patients who present after an intentional exposure or ingestion. (See Chapter 58, page 253.) 27. Brain perfusion pressure generally equals: ■Mean arterial pressure minus intracranial pressure □Diastolic blood pressure minus intracranial pressure □Intracranial blood pressure minus systolic blood pressure □Systolic blood pressure minus diastolic blood pressure description The perfusion pressure of the brain (cerebral perfusion pressure [CPP]) is equal to the pressure of blood entering the cranium (mean arterial pressure [MAP]) minus the ICP, in most cases. (See Chapter 63, page 296.) 28. Severe traumatic brain injury is characterized by a Glasgow Coma Score (GCS) of: □0 □1-3 ■3-8 □9-12 description The hallmark of severe TBI is coma (GCS score 3-8). Often, coma is seen immediately after the injury and is sustained. In some cases, such as with an epidural hematoma, a child may be alert at presentation but the condition may deteriorate after a period of hours. A similar picture can be seen in children with diffuse swelling, in whom a talk-and-die scenario has been described. Clinicians also should not be lulled into underappreciating the potential for deterioration of a child with moderate TBI (GCS score 9-12) with a significant contusion, because progressive swelling can potentially lead to devastating complications. In the comatose child with severe TBI, the second key clinical manifestation is the development of intracranial hypertension. Increased ICP can be appropriately managed only with continuous ICP monitoring. The development of brain swelling is progressive. Significantly raised ICP (>20 mm Hg) can occur early after severe TBI, but peak ICP generally is seen at 48-72 hr. Need for ICP-directed therapy may persist for longer than a week. A few children have coma without increased ICP, resulting from axonal injury or brainstem injury. (See Chapter 63, page 298.)29. Children with moderate to severe traumatic brain injury require intracranial pressure monitoring and treatment in the critical care unit to prevent progressive swelling. First-line therapies include all of the following EXCEPT: ■Hypothermia □Head in midline position □Sedation and analgesia □Controlled mechanical ventilation □Mannitol therapy for ICP >20 mm Hg description First-tier therapy includes elevation of the head of the bed, ensuring midline positioning of the head, controlled mechanical ventilation, and sedation and analgesia (i.e., benzodiazepines and narcotics). If neuromuscular blockade is needed, it may be desirable to monitor the EEG continuously because status epilepticus can occur; this complication will not be recognized in a paralyzed patient and is associated with raised ICP and unfavorable outcome. If a ventricular rather than parenchymal catheter is used to monitor ICP, therapeutic CSF drainage is available. Other first-tier therapies include the osmolar agents mannitol and hypertonic saline given in response to ICP spikes. If ICP remains refractory to treatment, careful reassessment of the patient is needed to rule out unrecognized hypercarbia, hypoxemia, fever, hypotension, hypoglycemia, pain, and seizures. Repeat imaging should be considered to rule out a surgical lesion. Guidelines-based second-tier therapies for refractory raised ICP are available, but evidence favoring a given second-tier therapy is limited. In some centers, decompressive craniectomy is used. Others use a pentobarbital infusion. Mild hypothermia (32-34°C) to control refractory ICP can be induced and maintained by means of surface cooling. Refractory raised ICP can also be treated with hyperventilation (PaCO2 = 25-30 mm Hg). Other second-tier therapies such as lumbar CSF drainage are options. (See Figure 63-12; also Chapter 63, page 300.) 30. Which of the following statements regarding cooling treatment for perinatal hypoxic ischemic encephalopathy is not true? □Candidates for cooling therapy have perinatal asphyxia, Apgar score of 0-3, acidosis, and neurologic dysfunction □Coagulopathy is a contraindication for cooling therapy □Goal core temperature is 32-34°C during cooling therapy. □During cooling therapy, shivering should be prevented with sedation and neuromuscular blockade ■After 72 hours, the patient should be rapidly rewarmed to 36°Cdescription Similarly, in perinatal asphyxia, fetal acidosis, an Apgar score of 0-3 after 5 min, neurologic dysfunction, and/or abnormal EEG findings are criteria for use of cooling therapy in term newborn infants. Exclusion criteria have included coagulopathy, bleeding, and hemodynamic instability. According to the American Heart Association (AHA) guidelines (predominantly for adults after a cardiac arrest when the initial event was associated with ventricular fibrillation), cooling should be initiated as soon as possible after return of spontaneous circulation but may be beneficial even if delayed (4-6 hr); it should be induced by means of surface cooling with cooling blankets; application of ice packs to the groin, axillae, and neck; use of wet towels; and fanning. Infusion of 20 mL/kg IV of ice-cold saline over 30 min can be considered in children and may reduce core temperature by approximately 2°C. If hypothermia is used in children, a temperature of 32-34°C should be used. The rewarming rate should be no greater than 1°C every 4-6 hr. In perinatal asphyxia, cooling should be maintained for 72 hr. Shivering should be prevented with sedation and neuromuscular blockade. Temperature should be continuously monitored. Hypothermia in children has been associated with an increased risk for neutropenia and sepsis. (See Chapter 63, page 302.) 31. First-line medications for status epilepticus include all of the following, EXCEPT: □Rectal diazepam □Intravenous lorazepam □Intravenous fosphenytoin □Intravenous phenobarbital ■Intravenous valproic acid description Several antiepileptic drugs have been advocated as first-line therapies for status epilepticus, including benzodiazepines (rectal diazepam, IV midazolam or lorazepam), phenytoin (or fosphenytoin), and barbiturates (phenobarbital). Therapy is adjusted for both symptoms and EEG evidence of seizures. In the PICU, for refractory cases, a continuous infusion of barbiturates and/or benzodiazepines may be necessary. For refractory cases that progress to this level of therapeutic intensity, respiratory support and hemodynamic monitoring and/or support should already be in place. As therapy escalates, continuous EEG monitoring should be considered to help titrate therapy. For refractory status epilepticus, newer therapies include mapping of the seizure focus followed by neurosurgical resection, IV lidocaine, or levetiracetam. (See Chapter 63, page 303.) 32. The following statements about stroke in children are true EXCEPT: □The most common causes of ischemic stroke in children are sickle cell disease and heart disease ■Atherosclerotic plaque migration is responsible for the majority of ischemic strokes □Stroke presents clinically with focal neurologic deficits or coma in children □A diagnosis of stroke requires CT or MRI findings□Differential diagnosis of stroke in children includes complex migraine, seizures, and encephalitis description The predominant causes of ischemic stroke in children are sickle cell disease and heart disease (either acquired or congenital), which are responsible for approximately 50% of strokes after the neonatal period. Ischemic strokes in children are generally not the result of atherosclerotic plaque migration, as they are in adults. Instead, damage to the intima of cerebral arteries can form a thrombotic nidus. In sickle cell disease, chronic turbulent blood flow likely leads to vascular damage. In intracerebral hemorrhage, blood vessel wall integrity is compromised, leading to extravasation of blood into the parenchyma or dural spaces. The usual pathology in children with heart disease is embolism from diseased valves (or intracardiac devices) and right-to-left shunts that leads to cerebrovascular occlusion. (See Chapter 63, page 303.) 33. Which of the following statements about ventilator-associated pneumonia (VAP) is NOT true? □VAP is multifactorial and causes include endotracheal tube colonization, aspiration of gastric secretions, and suppression of cough reflexes ■VAP is largely unpreventable □Fever, leukocytosis, and infiltrate on chest radiography support a diagnosis of VAP □Empirical treatment of VAP should include nosocomial pathogens description Elevation of the head of the bed to 30 degrees after initiation of mechanical ventilation and use of a protocol for oral decontamination during mechanical ventilation are two means of reducing the risk for VAP. The most effective strategy to minimize any ventilator complication is regular assessment of extubation readiness and liberation from mechanical ventilation as soon as clinically possible. (See Chapter 65, page 328.) 34. The initial ventilator settings are determined by: ■The patient's underlying disease □The patient's preferences □Standard order sets □Attempts to normalize the blood gases description The choice of mode of ventilation depends on how much ventilator-patient interaction is desired and the disease entity that is being treated. (See Chapter 65, page 327.) 35. Patients with severe forms of reactive airways disease (e.g., asthma) who require mechanical ventilation may benefit from which of the following initial ventilator parameters?□Rapid rates, short inspiratory times, and tidal volumes <6 mL/kg □Low rates, prolonged inspiratory/expiratory times, and low tidal volumes (<6 mL/kg) ■Low rates, prolonged inspiratory/expiratory times, and moderate tidal volumes (10-12 mL/kg) □Low rates, prolonged inspiratory/expiratory times, and high tidal volumes (>15 mL/kg) description In a patient with relatively normal lungs, an age-appropriate ventilator rate and a tidal volume of 7-10 mL/kg would be appropriate initial settings. Diseases associated with decreased time constants (decreased static compliance, e.g., ARDS, pneumonia, pulmonary edema) are best treated with small (6 mL/kg) tidal volume and relatively rapid rates (25-40 breaths/min). Diseases associated with prolonged time constants (increased airway resistance, e.g., asthma, bronchiolitis) are best treated with relatively slow rates and higher (10-12 mL/kg) tidal volume. (See Chapter 65, page 327.) 36. Per the IOM, high-quality health care by definition must be: □Timely and effective □Equitable and efficient □Safe and patient centered □A and C ■All of the above description To measure health care quality, the IOM has identified Six Dimensions of Quality, all of which relate to quality of care. The Six Dimensions of Quality are effectiveness, efficiency, equity, timeliness, patient safety, and patient-centered care. The IOM emphasizes the concept that all Six Dimensions of Quality need to be met for the provision of high-quality health care. Health care that maximizes outcomes but is not efficient (i.e., not cost-effective) is not quality care. Health care that is highly efficient but limits access also is not high quality. These concepts can be viewed as the overall value proposition—that is, the value created for a patient. (See e2-1.) 37. Which of the following is a step in the rapid cycle of improvement (PDSA)? □Perform □Define ■Study□Attend description The Model for Improvement can be implemented using a framework of rapid cycle of improvement also known as the Plan-Do-Study-Act (PDSA) cycle (Fig. 2-1). The PDSA cycle is typically aimed at testing small changes and then studying the results to plan and implement the next cycle of change (i.e., multiple PDSA cycles build on previous learning from PDSAs). Valuable information can be obtained from PDSA cycles that are successful and those that are not, to help plan the next iteration of the PDSA cycle. The PDSA cycle specifically requires that improvements be data driven. This is important because many clinicians attempt to make changes for improvement in their practice but do not emphasize the importance of data collection. (See e2-3.) 38. Developing a culture of safety relies on all of the following concepts EXCEPT: □De-emphasizing hierarchy and encouraging contributions of all members of the health care team □Excellent communication including patient hand-outs □Application of human factors engineering to systems and processes ■Discouraging anonymity in the reporting of adverse events description The biggest challenge in making the health system safer is changing the culture from one of treating errors as personal failures to one of treating errors as opportunities to improve the system. Organizations need to foster a culture of learning in which each individual will feel accountable for ensuring a safe and quality program, communication is open, and teamwork is valued. Reporting of errors should be valued, reports of adverse events should be handled confidentially, and those who report errors should be protected from discovery. Developing a culture of learning involves the compassionate and appropriate disclosure of system failures and medical errors to patients and families. (See e2-6). 39. A 4 yr old girl sustained a 40% 2nd- and 3rd-degree total body surface area (BSA) burn from scalding hot water. Of the following, the most therapeutic approach is: □Aggressive use of topical antibacterial agents with frequent dressing changes □Use of enzymatic debridement ointment ■Excision of the burn wounds and grafting □Use of topical analgesics description Deep 2nd-degree burns of >10% of BSA benefit from early excision and grafting. To improve outcome, sequential excision and grafting of 3rd-degree and deep 2nd-degree burns is required in children with large burns. Prompt excision with immediate wound closure is achieved with autografts, which are often meshed to increase the efficiency of coverings. (See Chapter 68, page 353.)40. A 10 yr old boy sustained 30% BSA burns and had been requiring dressing changes for physical therapy. Which of the following regimens will provide the best pain management? □IV morphine bolus □Oral ibuprofen □Oral acetaminophen ■Oral morphine and oral lorazepam description From the onset of treatment, preemptive pain control during dressing changes is of paramount importance. Opiate analgesia, prescribed in an adequate dose and timed to cover dressing changes, is essential to comfort management. Anxiolytic medication added to the analgesic is usually helpful and has more than a synergistic effect. (See Chapter 68, page 355.) 41. Indications for admission to the hospital after a burn injury may include all of the following EXCEPT: □Suspected child abuse □Electric burns through an extremity □Perineal burns □Poor follow-up ■No tetanus immunization □Inhalation injury description Burns covering >10-15% of total BSA, burns associated with smoke inhalation, burns resulting from hightension (voltage) electrical injuries, and burns associated with suspected child abuse or neglect should be treated as emergencies, and the child hospitalized. Small 1st- and 2nd-degree burns of the hands, feet, face, perineum, and joint surfaces also require admission if close follow-up care is difficult to provide. Children who have been in enclosed-space fires and those who have face and neck burns should be hospitalized for at least 24 hr for observation for signs of central nervous system (CNS) effects of anoxia from carbon monoxide poisoning and pulmonary effects from smoke inhalation. (See Table 68-2, Chapter 68, page 349.) 42. A burn wound characterized by the absence of painful sensation, bleeding, or capillary refilling is best classified as:□First degree □Moderate to severe □Second degree □Midlevel ■Full thickness description Full-thickness, or 3rd-degree, burns involve destruction of the entire epidermis and dermis, leaving no residual epidermal cells to repopulate the damaged area. The absence of painful sensation and capillary filling demonstrates the loss of nerve and capillary elements. The wound cannot epithelialize and can heal only by wound contraction or skin grafting. (See Table 68-5, Chapter 68, page 351.) 43. Which of the following statements regarding predictive genetic testing is true? □Predictive testing is genetic testing done in a person who is symptomatic for a genetic disorder □Predictive testing in children is ethically acceptable if the parents desire it □Federal law prevents companies from denying disability insurance based on a positive genetic test ■If a person has a positive predictive genetic test for a disease, he/she may not ever develop that disease □None of the above description Predictive genetic testing involves performing a test in a person who is at risk for developing a genetic disorder (presymptomatic), usually on the basis of family history, yet who does not manifest signs or symptoms. A major caution with predictive testing is that the presence of a gene mutation does not necessarily mean that the disease will develop. Many of the disorders with age-dependent penetrance display incomplete penetrance. A person who inherits a mutation might never develop signs of the disorder. In the USA, the Genetic Information Nondiscrimination Act of 2008 protects individuals from genetic discrimination at the hands of health insurers and employers but does not extend protection against discrimination from providers of life, disability, or long-term care insurance. (See Chapter 72, page 377.) 44. Genetic counseling is indicated in which of the following clinical scenarios? □Abnormal prenatal quad screen □Infant born with hypoplastic left heart disease□History of multiple miscarriages □Two cousins planning to marry □Child diagnosed with cystic fibrosis ■All of the above description See Table 72-2, Indications for Genetic Counseling. (See Chapter 72, page 378.) 45. Which statement regarding treatment of genetic disorders is NOT true? ■Physiologic therapy for genetic disease such as PKU is curative if started early □Newborn screening is important because early identification of genetic disorders allows early treatment □Enzyme replacement is available for Gaucher disease and Pompe disease □A bone marrow transplant may potentially cure thalassemia major □Gene-transfer vehicles include viruses description Physiologic therapies attempt to ameliorate the phenotype of a genetic disorder by modifying the physiology of the affected individual. The underlying defect itself is not altered by treatment. Physiologic therapies are used in the treatment of inborn errors of metabolism. These include dietary manipulation, such as avoiding phenylalanine by persons with phenylketonuria; coenzyme supplementation for some patients with methylmalonic acidemia and mitochondrial diseases; stimulation of alternative pathways to excrete ammonia for those with urea cycle disorders; bisphosphonate treatment for those with osteogenesis imperfecta to reduce bone fractures; and avoiding cigarette smoking by persons with α1-antitrypsin deficiency. Physiologic treatments can be highly effective, but they usually need to be maintained for a lifetime because they do not affect the underlying genetic disorder. Many of these treatments are most effective when begun early in life before irreversible damage has occurred. This is the rationale for comprehensive newborn screening for inborn errors of metabolism. (See Chapter 72, page 379.) 46. Which statement regarding genetic disorders of metabolism is NOT true? ■In severe disorders, the affected infant may be sick at birth □Most genetic metabolic diseases are treatable □The majority of genetic metabolic disease have autosomal recessive inheritance□Early diagnosis is crucial to good prognosis for most disorders □Tandem mass spectrometry may identify a large number of disorders with just a few drops of blood description In genetic disorders of metabolism, the affected infant is normal at birth and becomes symptomatic later in life. This differentiates these infants from those who appear sick at birth due to birth trauma, intrauterine insults, chromosomal abnormalities, or other genetic diseases. Severe forms of genetic disorders usually become clinically apparent in the newborn period or shortly thereafter. The majority of conditions are inherited as autosomal recessive traits. Most of the genetic metabolic conditions can be controlled successfully by some form of therapy, and a few can be potentially cured by the use of bone marrow or liver transplants. This underlines the importance of early diagnosis, which can be achieved through screening of all newborn infants. Tandem mass spectrometry (MS/MS) requires a few drops of blood to be placed on a filter paper and mailed to a central laboratory for assay. A large number of genetic conditions can be identified by this method. (See Chapter 78, page 416). 47. Signs and symptoms of inborn errors of metabolism include all of the following EXCEPT: □Vomiting ■Diarrhea □Lethargy □Poor feeding □Seizures description Pediatricians should familiarize themselves with early manifestations of genetic metabolic disorders, because (1) severe forms of some of these conditions may cause symptoms before the results of screening studies become available and (2) the current screening methods, although quite extensive, identify a small number of all inherited metabolic conditions. In the newborn period, the clinical findings are usually nonspecific and similar to those seen in infants with sepsis. A genetic disorder of metabolism should be considered in the differential diagnosis of a severely ill newborn infant, and special studies should be undertaken if the index of suspicion is high. Signs and symptoms such as lethargy, poor feeding, convulsions, and vomiting may develop as early as a few hours after birth. (See Chapter 78, page 416 and Fig. 78-1.) 48. Initial laboratory studies to investigate for metabolic disease in an ill infant should include: □Lactate, glucose, bicarbonate □Glucose, calcium, pH □Sodium, glucose, bicarbonate ■pH, bicarbonate, ammonia□Complete blood cell count, sodium, potassium description Measurements of serum concentrations of ammonia, bicarbonate, and pH are often very helpful initially in differentiating major causes of genetic metabolic disorders (see Fig. 78-1). An elevated blood ammonia level is usually caused by defects of urea cycle enzymes. Infants with elevated blood ammonia levels from urea cycle defects commonly have normal serum pH and bicarbonate values; without measurement of the blood ammonia level their defect may remain undiagnosed and they may succumb to their disease. Elevation of serum ammonia levels also is observed in some infants with certain organic acidemias. These infants are severely acidotic because of accumulation of organic acids in body fluids. When blood ammonia, pH, and bicarbonate values are normal, other aminoacidopathies (e.g., hyperglycinemia) or galactosemia should be considered; galactosemic infants also may manifest cataracts, hepatomegaly, ascites, and jaundice. (See Chapter 78, page 417). 49. A 2 day old boy manifests poor feeding, vomiting, and lethargy leading to coma. Laboratory data reveal respiratory alkalosis and hyperammonemia. The urine orotic acid level is also elevated. The most likely diagnosis is: □Methylmalonic acidemia □Carbamoylphosphate synthase deficiency ■Ornithine transcarbamylase (OTC) deficiency □Galactosemia □Reye syndrome description Many genetic disorders of metabolism increase plasma ammonia. In neonatal hyperammonemia, most of the symptoms are related to brain dysfunction due to the elevated ammonia. The affected infant is normal at birth but becomes symptomatic within a few days of protein feeding. Refusal to eat, vomiting, tachypnea, and lethargy can quickly progress to a deep coma. Convulsions are common. See Figure 79-13 for an algorithm to diagnose the cause of hyperammonemia. In the case of OTC deficiency, laboratory studies will not demonstrate acidosis. A marked increase in urinary orotic acid distinguishes OTC deficiency from other disorders. (See Figure 79-13 in Chapter 79, page 449.) 50. For most lysosomal storage disorders, carrier identification and prenatal diagnosis are available; a specific diagnosis is essential to permit genetic counseling. Which of the following disorders is X-linked? □Niemann-Pick disease ■Fabry disease□Tay-Sachs disease □Krabbe disease □Gaucher disease description For all of the lysosomal storage disorders, inheritance is autosomal recessive except for X-linked Fabry disease. (See Chapter 80, page 483.) 51. GM1 gangliosidosis is characterized by all of the following EXCEPT: □Psychomotor retardation □Angiokeratomas □Hepatosplenomegaly □Frontal bossing ■Peripheral neuropathy description The clinical manifestations of the infantile form of GM1 gangliosidosis may be evident in the newborn infant as hepatosplenomegaly, edema, and skin eruptions (angiokeratomas). It most frequently presents in the first 6 mo of life with developmental delay followed by progressive psychomotor retardation and the onset of tonic-clonic seizures. A typical facies is characterized by low-set ears, frontal bossing, a depressed nasal bridge, and an abnormally long philtrum. Up to 50% of patients have a macular cherry-red spot. Hepatosplenomegaly and skeletal abnormalities similar to those of the mucopolysaccharidoses, including anterior beaking of the vertebrae, enlargement of the sella turcica, and thickening of the calvarium, are present. (see Chapter 80, page 483.) 52. A 4 mo old girl presents with developmental delay, an exaggerated startle response to loud noise, and macrocephaly. On physical examination, the child has decreased eye contact and a cherry-red spot in each retina. The most likely diagnosis is: ■GM2 gangliosidosis □Gaucher disease □Fabry disease □Galactosemia □Glycogen storage disease, type Idescription The GM2 gangliosidoses include Tay-Sachs disease and Sandhoff disease; each results from the deficiency of β-hexosaminidase activity and the lysosomal accumulation of GM2 gangliosides, particularly in the central nervous system. The clinical manifestations of Sandhoff disease are similar to those for Tay-Sachs disease. The diagnosis of infantile TaySachs disease and Sandhoff disease is usually suspected in an infant with neurologic features and a cherry-red spot. Affected infants usually develop normally until 4 to 5 mo of age when decreased eye contact and an exaggerated startle response to noise (hyperacusis) are noted. Macrocephaly, not associated with hydrocephalus, may develop. In the 2nd yr of life, seizures develop that may be refractory to anticonvulsant therapy. Neurodegeneration is relentless, with death occurring by the age of 4 or 5 yr. (See Chapter 80, page 482.) 53. A 15 yr old presents with chronic fatigue and severe bone pain of 1 year's duration. He has hepatosplenomegaly and a normal retinal examination. Laboratory studies reveal normocytic anemia and thrombocytopenia. Radiographs of the distal femur reveal Erlenmeyer flask deformities. The most likely diagnosis is: □Lymphoma ■Gaucher disease □Sandhoff disease □GM3 gangliosidosis □Sickle cell anemia description Gaucher disease is a multisystemic lipidosis characterized by hematologic abnormalities, organomegaly, and skeletal involvement, the latter usually manifesting as bone pain and pathologic fractures. Clinical manifestations of type 1 Gaucher disease have a variable age at onset, from early childhood to late adulthood, with most symptomatic patients presenting by adolescence. At presentation, patients may have bruising from thrombocytopenia, chronic fatigue secondary to anemia, hepatomegaly with or without elevated liver function test results, splenomegaly, and bone pain. Most patients develop radiologic evidence of skeletal involvement, including an Erlenmeyer flask deformity of the distal femur. (See Chapter 80, page 487.) 54. Fabry disease is characterized by all of the following EXCEPT: □Acroparesthesias □Corneal opacities □Cardiomyopathy ■Mental retardation□Angiokeratomas description Fabry disease is an X-linked inborn error of glycosphingolipid metabolism characterized by angiokeratomas (telangiectatic skin lesions), hypohidrosis, corneal and lenticular opacities, acroparesthesias, and vascular disease of the kidney, heart, and/or brain. (See Chapter 80, page 489.) 55. A 14 mo old girl presents with irritability, poor walking, genu recurvatum, and hypotonia. Physical examination reveals absent deep tendon reflexes. Laboratory data reveal an increased cerebrospinal fluid protein level and decreased nerve conduction velocities. The most likely diagnosis is: ■Metachromatic leukodystrophy □I cell disease □GM3 gangliosidosis □Fabry disease □Neuromyopathic Gaucher disease description The clinical manifestations of the late infantile form of metachromatic leukodystrophy, which is most common, usually present between 12 and 18 mo of age as irritability, inability to walk, and hyperextension of the knee, causing genu recurvatum. The clinical progression of the disease relates to the pathologic involvement of both central and peripheral nervous system, giving a mixture of upper and lower motor neuron and cognitive and psychiatric signs. Deep tendon reflexes are diminished or absent. Gradual muscle wasting, weakness, and hypotonia become evident and lead to a debilitated state. As the disease progresses, nystagmus, myoclonic seizures, optic atrophy, and quadriparesis appear, with death in the 1st decade of life. On evaluation, decreased nerve conduction velocities, increased cerebrospinal fluid protein, metachromatic deposits in sampled segments of sural nerve, and metachromatic granules in urinary sediment are all suggestive of the disorder. (See Chapter 80, page 490.) 56. A 15 yr old Ashkenazi Jewish girl is seen because of chronic fatigue. On examination, she seems pale and thin and has a somewhat large abdomen. Her spleen is felt in the iliac fossa. She is mentally alert and has a history of normal development and normal school performance. Her blood cell count shows hemoglobin, 9.0 g/dL and a white blood cell count of 3,000/mm3, with normal differential cell count and no abnormal cells. Platelet count is 60,000/μL. The most likely diagnosis is: □Tay-Sachs disease □Niemann-Pick disease type A ■Gaucher disease type I□Mucolipidosis type IV □Canavan disease description Clinical manifestations of type I Gaucher disease have a variable age at onset, from early childhood to late adulthood, with most symptomatic patients presenting by adolescence. Type I, which accounts for 99% of cases, has a striking predilection for Ashkenazi Jews. Gaucher disease should be considered in the differential diagnosis of patients with unexplained organomegaly, who bruise easily, have bone pain, or have a combination of these conditions. Evaluation may show bruising from thrombocytopenia, chronic fatigue secondary to anemia, hepatomegaly with or without elevated liver function test results, splenomegaly, and bone pain. (See Chapter 80, page 487.) 57. A 7 mo old boy has been healthy and developing normally since birth. His mother now reports that he has decreased eye contact with her, even during feedings. The infant also startles very easily when there is a loud noise in the house. Of the following, the most appropriate diagnostic test to confirm the etiology of these findings is the measurement of: ■Leukocyte β-hexosaminidase A activity □Serum concentration of amino acids □Serum concentration of ammonia □Urinary mucopolysaccharides □Urinary organic acids description Patients with the infantile form of GM2 gangliosidoses have clinical manifestations in infancy including loss of motor skills, increased startle reaction, and macular pallor and retinal cherry-red spots. Affected infants usually develop normally until 4 to 5 mo of age when decreased eye contact and an exaggerated startle response to noise (hyperacusis) are noted. Macrocephaly, not associated with hydrocephalus, may develop. Definitive diagnosis is made by determination of β-hexosaminidase A and B activities in peripheral leukocytes. The two GM2 gangliosidoses are distinguished by the enzymatic assay, because in Tay-Sachs disease only the β-hexosaminidase A isozyme is deficient, whereas in Sandhoff disease both the β-hexosaminidase A and B isozymes are deficient. (See Chapter 80, page 485.) 58. A 3 yr old boy was normal at birth but developed progressive coarsening of the face and developmental delay. In addition to coarse facies and mental retardation, the physical examination reveals a cardiac systolic regurgitant murmur, hepatomegaly, joint stiffness, and short stature. CT scan reveals hydrocephalus. There is no corneal clouding. All affected family members have been boys. The most likely diagnosis is: □Hurler syndrome□Galactosemia □Metachromatic leukodystrophy ■Hunter syndrome □Sanfilippo syndrome description Hunter disease (MPS II) is an X-linked disorder and manifests almost exclusively in males. It has been observed in a few females and this is explained by skewed inactivation of the X chromosome carrying the normal gene. Patients with severe MPS II have features similar to those of Hurler disease except for the lack of corneal clouding and the somewhat slower progression of somatic and central nervous system deterioration. Coarse facial features, short stature, dysostosis multiplex, joint stiffness, and mental retardation manifest between 2 and 4 yr of age. (See Chapter 82, page 511.) 59. Hurler disease is characterized by all of the following EXCEPT: □Hepatosplenomegaly □Coarse facies □Dysostosis multiplex ■X-linked inheritance □Corneal clouding description Diagnosis of Hurler disease is usually made between 6 and 24 mo of age with evidence of hepatosplenomegaly, coarse facial features, corneal clouding, large tongue, prominent forehead, joint stiffness, short stature, and skeletal dysplasia known as dysostosis multiplex. Acute cardiomyopathy has been found in some infants younger than 1 yr of age. Inheritance is autosomal recessive. (See Chapter 82, page 511.) 60. According to the International Classification of Diseases, major causes of U.S. infant mortality include all of the following EXCEPT: □Sudden infant death syndrome □Disorders relating to prematurity □Congenital malformations□Disorders relating to maternal complications of pregnancy ■Nonaccident