Its Friday
A 2-year-old child is brought to a community clinic by her grandmother because of increasing irritability and developmental concerns. The child recently immigrated from another country and has never established consistent pediatric care. The grandmother reports that the child says very few words, has difficulty following simple commands, and often falls when trying to run. Physical examination demonstrates mild hypotonia, microcephaly, fair hair and skin compared with family members, and an erythematous rash over the buttocks and lowerback. A noticeable musty odor is present. Laboratory studies show a plasma phenylalanine concentration of 1300 μmol/L (normal <120μmol/L) and decreased plasma tyrosine.
Which of the following biochemical abnormalities most directly contributes to this patient's neurologic symptoms?
A. Impaired synthesis of serotonin and dopamine within the CNS
B. Defective degradation of branched-chain amino acids
C. Impaired beta-oxidation of medium-chain fatty acids
D. Decreased conversion of tyrosine to fumarate
E. Accumulation of homogentisic acid within neural tissue
A. Impaired synthesis of serotonin and dopamine within the CNS
A 2-year-old child is brought to clinic because of developmental delay and behavioral concerns. Family members have dark hair and olive-colored skin, but the child has very light hair and a much paler complexion. Physical examination reveals hypotonia and mildmicrocephaly. Laboratory studies demonstrate markedly elevated plasma phenylalanine and decreased plasma tyrosine. The physicianexplains that the pigmentation abnormalities are directly related to deficiency of a compound derived from tyrosine.
Which of the following substances is most likely decreased in this patient?
A. Dopamine
B. Melanin
C. Acetyl-CoA
D. Carnitine
E. Ketone bodies
B. Melanin
A previously healthy 4-year-old girl develops vomiting and decreased oral intake after a viral illness. Her parents report she slept muchlonger than usual and was difficult to awaken the following morning. Laboratory testing reveals severe hypoglycemia and very low serumketones.
Which metabolic process is most likely impaired?
A. Glycogenolysis
B. Glycolysis
C. Beta-oxidation of fatty acids
D. Gluconeogenesis
E. Pentose phosphate pathway
C. Beta-oxidation of fatty acids
A newborn is diagnosed with classic PKU through state-sponsored screening. The family asks why dietary treatment must beginimmediately despite the baby appearing healthy.
Early treatment primarily prevents which complication?
A. Renal failure
B. Cirrhosis
C. Irreversible neurologic injury
D. Cardiomyopathy
E. Pancreatitis
C. Irreversible neurologic injury
newborn appears healthy following an uncomplicated pregnancy and delivery. Routine newborn screening identifies elevated concentrations of octanoylcarnitine (C8-carnitine). Further evaluation demonstrates elevated urinary dicarboxylic acids. The infant isdiagnosed with an inherited metabolic disorder and the parents are educated about avoiding prolonged fasting.
Which of the following metabolic consequences would most likely occur during an extended fast if this disorder were left untreated?
A. Hyperketotic hypoglycemia
B. Hypoketotic hypoglycemia
C. Isolated hyperammonemia
D. Severe metabolic alkalosis
E. Elevated circulating ketone bodies with normal glucose
B. Hypoketotic hypoglycemia
A newborn screening panel demonstrates elevated concentrations of octanoylcarnitine (C8-carnitine). Subsequent testing confirms adisorder affecting fatty acid utilization during fasting. Parents are counseled extensively regarding feeding schedules and avoidance ofprolonged fasting.
Accumulation of C8-carnitine most directly reflects failure of which process?
A. Oxidation of medium-chain fatty acids
B. Oxidation of branched-chain amino acids
C. Conversion of phenylalanine to tyrosine
D. Carnitine transport across the plasma membrane
E. Ketone body utilization
A. Oxidation of medium-chain fatty acids
A child with MCAD deficiency is admitted after prolonged fasting. Laboratory testing reveals blood glucose of 32 mg/dL and absent serumketones.
Which metabolic product is most directly reduced because of the enzyme deficiency?
A. Acetyl-CoA
B. Lactate
C. Pyruvate
D. Citrate
E. Glycogen
A. Acetyl-CoA
A newborn has elevated C8-carnitine detected through tandem mass spectrometry.
Why are acylcarnitines formed?
A. To increase ketone production
B. To facilitate urinary excretion of toxic acyl groups
C. To increase gluconeogenesis
D. To stimulate beta oxidation
E. To increase mitochondrial ATP production
B. To facilitate urinary excretion of toxic acyl groups
A 4-year-old girl with a known inborn error of metabolism develops an acute febrile illness and is treated for otitis media. Several days later she develops vomiting, poor oral intake, lethargy, and progressive weakness. Overnight she becomes difficult to arouse. Laboratorystudies reveal severe hypoglycemia, elevated C8-carnitine concentrations, absent serum ketones, mild hyperammonemia, and elevatedserum transaminases.
Which of the following is the primary reason this patient developed neurological dysfunction?
A. Inability to utilize glycogen stores
B. Deficiency of phenylalanine hydroxylase activity
C. Failure to generate sufficient ATP and ketone bodies during fasting
D. Excess production of branched-chain ketoacids
E. Decreased synthesis of catecholamine neurotransmitters
C. Failure to generate sufficient ATP and ketone bodies during fasting
A 4-year-old child with a known metabolic disorder develops otitis media and fever. Over several days she stops eating well and beginsvomiting. Her mother notices increasing lethargy and brings her to the emergency department. Laboratory testing demonstrateshypoglycemia, low ketones, mild hyperammonemia, and elevated AST and ALT.
Which feature of the illness most likely precipitated this metabolic decompensation?
A. Increased insulin secretion
B. Increased hepatic glycogen stores
C. Reduced energy requirements
D. Increased metabolic demands combined with reduced caloric intake
E. Increased ketone production
D. Increased metabolic demands combined with reduced caloric intake