A 12-year-old boy is brought to the office due to gait instability and pruritic skin rash for the past several weeks. His mother reports that he has also been irritable and had loose stools during this time. The patient's childhood development has been unremarkable except for several episodes of similar skin rash that resolved spontaneously. Examination shows scaly, erythematous skin lesions in sun-exposed areas and cerebellar ataxia. Laboratory evaluation shows increased levels of neutral amino acids in the urine. This patient's symptoms would most likely respond to which of the following supplements?

Question

A 12-year-old boy is brought to the office due to gait instability and pruritic skin rash for the past several weeks.  His mother reports that he has also been irritable and had loose stools during this time.  The patient's childhood development has been unremarkable except for several episodes of similar skin rash that resolved spontaneously.  Examination shows scaly, erythematous skin lesions in sun-exposed areas and cerebellar ataxia.  Laboratory evaluation shows increased levels of neutral amino acids in the urine.  This patient's symptoms would most likely respond to which of the following supplements?

Quizplus · Accepted Answer

This patient likely has Hartnup disease, an autosomal recessive metabolic disorder caused by inactivating mutations affecting the neutral amino acid transporter. This results in impaired transport of neutral amino acids, particularly tryptophan, in the small intestine and proximal tubule of the kidney. Tryptophan is an essential amino acid and a precursor for niacin, serotonin, and melatonin. Conversion of tryptophan to niacin is responsible for the generation of up to half of the nicotinamide adenine dinucleotide (NAD+) required for redox reactions; the clinical manifestations of Hartnup disease are primarily due to niacin deficiency. Patients present with intermittent attacks of pellagra-like skin eruptions (development of a red, rough rash following sun exposure) and cerebellar ataxia in early childhood that become less severe with increasing age. The diagnosis is confirmed by detecting excessive amounts of neutral amino acids (alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine, and tryptophan) in the urine (neutral aminoaciduria). A high-protein diet along with daily niacin or nicotinamide supplementation generally results in significant symptom improvement. (Choice A) Ascorbate (vitamin C) is a water-soluble vitamin required for hydroxylation of proline and lysine residues during collagen synthesis. Deficiency results in scurvy, a disease characterized by bone pain, easy bruising, and poor wound healing. (Choice B) Both folic acid and vitamin B₁₂ deficiencies result in a megaloblastic anemia. However, neurologic manifestations of subacute combined degeneration of the posterior and lateral columns are specific to vitamin B₁₂ deficiency. (Choice D) Pyridoxine (vitamin B₆) acts as a coenzyme in the decarboxylation and transamination of amino acids, including the metabolism of tryptophan to niacin. Deficiency of pyridoxine leads to anemia, peripheral neuropathy, and dermatitis. Supplementation in Hartnup disease is not effective due to underlying tryptophan malabsorption. (Choice E) The coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) form the prosthetic groups of several enzymes important in electron transport; both are synthesized from riboflavin (vitamin B₂). Clinical features of deficiency include sore throat, stomatitis, glossitis, normocytic anemia, and seborrheic dermatitis. (Choice F) Thiamine use by the body is maximal in states of accelerated carbohydrate metabolism because thiamine acts as a cofactor for the enzymes transketolase (pentose phosphate pathway), α-ketoglutarate dehydrogenase (TCA cycle), and pyruvate dehydrogenase (forms acetyl-CoA). (Choice G) Tocopherol (vitamin E) is a fat-soluble vitamin that functions as a scavenger of free radicals (antioxidant). Deficiency of vitamin E is rare but can result in neurologic dysfunction (ataxia, hyporeflexia, loss of sensation) as well as hemolytic anemia. Educational objective: Hartnup disease is caused by impaired transport of neutral amino acids in the small intestine and proximal tubule of the kidney. Symptoms include pellagra-like skin eruptions and cerebellar ataxia, which occur as a result of niacin deficiency. The diagnosis can be confirmed through detection of excessive amounts of neutral amino acids in the urine. __________ References: Hartnup disease. (http://www.ncbi.nlm.nih.gov/pubmed/4237364) Hartnup disorder: unraveling the mystery. (http://www.ncbi.nlm.nih.gov/pubmed/15681018)

A 12-Year-Old Boy Is Brought to the Office Due to Gait