Review Question - QID 106622

The young boy is presenting with pellagra-like symptoms due to Hartnup disease. Niacin deficiency would present with similar symptoms.

Hartnup disease is an aminoaciduria that results from mutations in the SLC6A19 gene which encodes a sodium-dependent/chloride independent neutral amino acid transporter primarily located in the intestines and kidney. This deficiency leads to a decrease in uptake of neutral amino acids (valine, threonine, phenylalanine, isoleucine, leucine, glutamine, alanine, tryptophan, asparagine, histidine, serine, and tyrosine) from the intestines and decreased reabsorption in the kidney. Since nicotinamide can be made from tryptophan, the symptoms of Hartnup disease result from a deficiency of nicotinamide, leading to a pellagra-like condition of dermatitis, diarrhea, and dementia.

Bröer reviews Hartnup disease, an autosomal disease first discovered in 1956, characterized by a neutral aminoaciduria accompanied by a photo-sensitive rash and cerebellar ataxia. The disease is caused by mutations in the B0AT1 neutral amino acid transporter encoded by the gene SLC6A19. To date there are 21 documented mutations in 20 families that result in Hartnup disease.

Bröer, Cavanaugh, and Rasko discuss that there are four different types of amino acid transporters in the kidney based on the aminoacidurias that are produced. The first is cystinuria, which is due to a defect in the transporter for cationic amino acids and cystine transport. The second aminoaciduria is Hartnup's disease, discussed above. The third aminoaciduria is iminoglycinuria, which is due to a defective transporter for proline and glycine. Finally, there is dicarboxylic aminoaciduria, which is due to a defective transporter for anionic amino acids.

Figure A demonstrates the photosensitivity pellagra-like dermatitis seen in Hartnup disease. Illustration A and B show the Hartnup skin rash in sun exposed areas of a 10-year-old girl that has crusted over and formed hyperpigmented plaques.

Incorrect Answers:
Answer 1: Thiamine deficiency is typically seen in the setting of alcoholism or malnutrition. Deficiency can result in several syndromes such as Wernicke syndrome, Korsakoff syndrome or beriberi.

Answer 2: Riboflavin deficiency is seen in severe malnutrition, and symptoms include cheilosis, corneal vascularization, and a magenta colored tongue.

Answer 4: Pyridoxine deficiency is seen when taking isoniazid, oral contraceptives, or in chronic alcoholism. Symptoms include convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia, cheilosis, or stomatitis.

Answer 5: Cobalamin deficiency can be seen in pernicious anemia, gastric bypass surgery, resection of the terminal ileum, Crohn's disease, and vegan diets. Symptoms include macrocytic, megaloblastic anemia, and paraesthesias.