A 4-day-old boy born to a 23-year-old woman is brought to the office for evaluation of poor feeding and vomiting. The pregnancy was uneventful and the mother had a normal delivery. Family history is noncontributory. The patient's temperature is 37.2 C (99 F), blood pressure is 60/30 mm Hg, pulse is 110/min, and respirations are 56/min. Physical examination reveals a lethargic newborn with exaggerated deep tendon reflexes and clonus. Further investigation reveals that the patient has an inherited condition that results in impaired transport of ornithine from the cytosol to the mitochondria. Nutritional restriction of which of the following substances can improve this patient's condition?

Question

A 4-day-old boy born to a 23-year-old woman is brought to the office for evaluation of poor feeding and vomiting.  The pregnancy was uneventful and the mother had a normal delivery.  Family history is noncontributory.  The patient's temperature is 37.2 C (99 F), blood pressure is 60/30 mm Hg, pulse is 110/min, and respirations are 56/min.  Physical examination reveals a lethargic newborn with exaggerated deep tendon reflexes and clonus.  Further investigation reveals that the patient has an inherited condition that results in impaired transport of ornithine from the cytosol to the mitochondria.  Nutritional restriction of which of the following substances can improve this patient's condition?

Quizplus · Accepted Answer

11ec160b_36c1_bb80_9249_6188ae0f4b9b_MD0001_00 Impaired transport of ornithine into the mitochondria can be caused by ornithine translocase deficiency, which results in a defect in the hepatic urea cycle. The urea cycle converts ammonia, which is generated from the catabolism of amino acids, into urea for excretion in urine. Urea cycle defects cause ammonia to accumulate in the blood, resulting in progressive lethargy, vomiting, seizures, and cerebral edema (may cause hyperreflexia and abnormal posturing when severe) in infancy and early childhood; milder defects caused by partial enzyme deficiencies may not manifest until adulthood. Effective treatment of urea cycle disorders requires balancing dietary protein intake and metabolic requirements. Protein restriction is the main treatment for urea cycle disorders, such that the body receives the essential amino acids needed for growth and development but not in excess such that excessive ammonia is formed. Medications that provide an alternate pathway to excrete nitrogen (eg, phenylacetate) are also used to help remove ammonia from the blood. (Choice A) Restriction of branched-chain amino acids (eg, valine, leucine, isoleucine) is used to treat maple syrup urine disease (branched-chain alpha-ketoacid dehydrogenase deficiency) and propionic acidemia (propionyl-CoA carboxylase). (Choice B) Fructose and sucrose restriction is the treatment for fructose 1-phosphate aldolase (aldolase B) deficiency. This condition causes vomiting and hypoglycemia in infants after fruit or juice is introduced. (Choice C) Galactose and lactose are excluded from the diet in patients with classic galactosemia (absent galactose-1-phosphate uridyltransferase). Galactosemia presents in neonates with jaundice, vomiting, poor feeding, lethargy, hypoglycemia, and galactose-1-phosphate accumulation. (Choice D) Medium-chain triglycerides are restricted in medium-chain acyl-CoA dehydrogenase deficiency, a condition characterized by lethargy, seizures, and hypoketotic hypoglycemia following a period of fasting. (Choice E) A phenylalanine-free diet is recommended in patients with phenylketonuria (phenylalanine hydroxylase deficiency). Failure to convert phenylalanine to tyrosine leads to accumulation of phenylalanine and intellectual disability if the condition is left untreated. (Choice G) Pyridoxine (vitamin B₆) can be used to treat homocystinuria, which is caused by a defect in vitamin B₆-dependent cystathionine synthase. This condition is characterized by elevated homocysteine levels, ectopia lentis, intellectual disability, Marfanoid body habitus, and increased occurrence of thromboembolic events. Educational objective: Ornithine transport into mitochondria is necessary for proper function of the urea cycle, which is the major disposal pathway for waste nitrogen generated by catabolism of amino acids. Urea cycle defects typically cause neurological damage due to the accumulation of ammonia. Protein restriction improves this condition by reducing the amount of amino acid turnover. __________ References: The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/25874378)

A 4-Day-Old Boy Born to a 23-Year-Old Woman Is Brought