Review Question - QID 107701

The clinical presentation is most consistent with hartnup disease, which results in low levels of niacin.

Niacin deficiency can be a result of poor nutritional intake, especially in those whose diet consists of primarily corn and cereal. Low niacin results in pellagra-like clinical manifestations, which have classically been described as the three D’s: dermatitis, diarrhea and dementia. Tryptophan is a precursor for niacin and instances where tryptophan levels are low can lead to symptoms such as in Hartnup disease.

Longo summarizes Hartnup disease as an autosomal recessive condition with a frequency of 1 in 24,000. Due to a defective transporter, neutral and aromatic amino acids are excreted in the urine at a rate 5-10 times greater than usual and have impaired migration through the intestines. The disease is diagnosed by detecting neutral amino acids in the urine. Treatment is with niacin replacement, which involves a protein-rich diet and daily nicotinamide supplementation.

Kleta et al. have confirmed that the gene critical for Hartnup disease is located on chromosome 5 using homozygosity mapping. The gene isolated is SLC6A19 which was found to be mutated in the original family identified with Hartnup disease. The SLC6A19 encodes for a neutral amino acid transporter that is found in intestinal and renal proximal tubules.

Illustration A depicts the classical symmetrical erythematous, blistering rash in sun exposed areas seen in niacin deficiency.

Incorrect Answers:
Answer 2: Vitamin A is important in phototransduction of the eye and deficiency may cause night blindness.
Answer 3: Vitamin K is important in the hepatic production of coagulation factors II, VII, IX, X, C and S. Deficiency can increase risk of bleeding.
Answer 4 and 5: Folate and B12 are important in DNA synthesis and deficiency can lead to megaloblastic anemia.