A 3-year-old boy is brought to the office due to abnormal motor development. He was born at 40 weeks gestation and had an unremarkable perinatal course. The boy developed normally during the first year of life. However, for the past 2 years, he has had progressive bilateral leg stiffness and abnormal involuntary movements. His cognitive and motor development is also delayed. There is no significant family history of neurological or muscular disorders. The patient's height, weight, and head circumference are below the 3rd percentile. Examination shows bilateral spastic paresis of his lower extremities and frequent choreoathetoid movements. Comprehensive laboratory testing reveals significantly elevated arginine levels in plasma and cerebrospinal fluid. The deficient enzyme in this patient is normally involved in the production of which of the following?

Question

A 3-year-old boy is brought to the office due to abnormal motor development.  He was born at 40 weeks gestation and had an unremarkable perinatal course.  The boy developed normally during the first year of life.  However, for the past 2 years, he has had progressive bilateral leg stiffness and abnormal involuntary movements.  His cognitive and motor development is also delayed.  There is no significant family history of neurological or muscular disorders.  The patient's height, weight, and head circumference are below the 3rd percentile.  Examination shows bilateral spastic paresis of his lower extremities and frequent choreoathetoid movements.  Comprehensive laboratory testing reveals significantly elevated arginine levels in plasma and cerebrospinal fluid.  The deficient enzyme in this patient is normally involved in the production of which of the following?

Quizplus · Accepted Answer

11ec160b_36c2_57c1_9249_558004728bb9_MD0001_00 This patient has features of arginase deficiency, including progressive development of spastic diplegia, abnormal movements, and growth delay in the setting of elevated arginine levels. Arginase is a urea cycle enzyme that produces urea and ornithine from arginine. Diagnosis is based on elevated arginine levels on plasma amino acid testing. Treatment of arginase deficiency consists of a low-protein diet devoid of arginine. Administration of a synthetic protein made of essential amino acids usually results in a dramatic decrease in plasma arginine concentration and an improvement in neurological abnormalities. Unlike other urea cycle disorders, patients with arginase deficiency have mild or no hyperammonemia. (Choice A) The amino acid derivative γ-aminobutyrate (GABA) is a well-known inhibitor of presynaptic transmission in the retina and central nervous system. GABA is formed from glutamate decarboxylation, a reaction catalyzed by glutamate decarboxylase. (Choice B) Glutamine is the major amino acid in the blood because it transports excess ammonia from peripheral tissues to the kidney. In the nephron, the amide nitrogen is hydrolyzed by glutaminase to regenerate glutamate and a free ammonium ion, which can then be excreted in the urine. (Choice C) Deficiencies of vitamins B₆, B₁₂, and folate (B₉) are associated with hyperhomocysteinemia, which in turn is associated with atherosclerosis and thrombotic events. (Choice D) Orotic acid is overproduced when a block in the urea cycle leads to excess carbamoyl phosphate, which is metabolized by dihydroorotate dehydrogenase to orotic acid. Excessive amounts of orotic acid are usually found in citrullinemia and ornithine transcarbamylase deficiency. These urea cycle disorders are also accompanied by hyperammonemia. (Choice E) Serotonin (5-hydroxytryptamine) is formed by the hydroxylation and decarboxylation of tryptophan by tryptophan hydroxylase. In addition, serotonin is degraded by monoamine oxidase and also undergoes neuronal reuptake. Educational objective: Arginase is a urea cycle enzyme that produces urea and ornithine from arginine. Arginase deficiency results in progressive spastic diplegia, growth delay, and abnormal movements. Treatment includes an arginine-free, low-protein diet. __________ References: Arginase-1 deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/26467175) Arginase Deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/20301338)

A 3-Year-Old Boy Is Brought to the Office Due to Abnormal