A 2-year-old boy is brought to the office by his parents. He is currently toilet-training during the day and at nighttime. After he urinated in the toilet last night, his parents forgot to flush the toilet and noticed that the boy's urine turned black overnight. The child has no significant past medical history and takes no medications. He can say 2-word sentences, follow 2-step directions, and jump with 2 feet off the ground. Examination shows a well-nourished child with no swelling or tenderness of any joints. Urinalysis results are as follows: Which of the following conversion pathways is most likely deficient in this patient?

Question

A 2-year-old boy is brought to the office by his parents.  He is currently toilet-training during the day and at nighttime.  After he urinated in the toilet last night, his parents forgot to flush the toilet and noticed that the boy's urine turned black overnight.  The child has no significant past medical history and takes no medications.  He can say 2-word sentences, follow 2-step directions, and jump with 2 feet off the ground.  Examination shows a well-nourished child with no swelling or tenderness of any joints.  Urinalysis results are as follows:  Which of the following conversion pathways is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_36c4_7aa7_9249_6bea36af2b71_MD0001_00 Alkaptonuria is an autosomal recessive disorder of tyrosine metabolism. Deficiency of homogentisic acid dioxygenase blocks homogentisic acid metabolism, preventing the conversion of tyrosine to fumarate. Homogentisic acid accumulates in the body and is excreted in the urine, imparting a black color to the urine if allowed to sit and undergo oxidation. In patients with alkaptonuria, the retained homogentisic acid selectively binds to collagen in connective tissues, tendons, and cartilage. This leads to "ochronosis," a blue-black pigmentation most evident in the ears, nose, and cheeks, and ochronotic arthropathy, which typically manifests during adulthood. (Choice A) Leucine is a branched-chain amino acid that is elevated in maple syrup urine disease. Isoleucine and valine are also increased. Impaired metabolism of these amino acids leads to cerebral edema, seizures, and a sweet smell of the urine. (Choice B) Conversion of phenylalanine to tyrosine is defective in phenylketonuria and usually occurs due to a defect in phenylalanine hydroxylase. Undiagnosed and untreated phenylketonuria results in significant intellectual disability not seen in this patient. (Choice C) Impaired renal cystine (a homodimer of cysteine) transport leads to cystinuria, a disease characterized by flank pain, hematuria, and renal stones in childhood or adolescence. (Choice E) Sickle cell anemia results from the substitution of valine for glutamic acid due to a single-nucleotide polymorphism. This mutation leads to loss of red cell elasticity, polymerization of sickle hemoglobin, and sickling of red blood cells, which results in vasoocclusive crises. Educational objective: Alkaptonuria is an autosomal recessive disorder in which the lack of homogentisic acid dioxygenase blocks the metabolism of tyrosine, leading to an accumulation of homogentisic acid. Clinical features include a black urine color when exposed to air, a blue-black pigmentation on the face, and ochronotic arthropathy. __________ References: Alkaptonuria. (http://www.ncbi.nlm.nih.gov/pubmed/25003018)

A 2-Year-Old Boy Is Brought to the Office by His