Snapshot A 12-year-old boy is brought to his pediatrician by his mother due to progressive confusion, diarrhea, and an itchy rash. He recovered from the flu about a week ago but was still feeling tired. Over the last 48 hours, he has had several episodes of diarrhea per day. On exam, he has a tremor, intermittent ataxia, and a rash (shown in the photograph). His mom says that he has previously had these kinds of symptoms usually after he has an illness. He is given nicotinic acid and placed on a high protein diet and quickly recovers. Introduction Amino acid clearance amino acids are freely filtered by the glomerulus into Bowman's capsule filtered amino acids are reabsorbed in the proximal tubule by sodium dependent co-transporters that are separated into multiple transporter types based on charge of amino acid size of amino acid in normal physiology all amino acids are reabsorbed by the tubule meaning that clearance of amino acids is zero amino acids are preserved for further use by the body defective reabsorption of amino acids by the proximal tubule can lead to Hartnup disease Hartnup deficiency deficiency of proximal renal tubule neutral amino acid transporters pathogenesis defective reabsorption of neutral amino acids leading to decreased serum concentrations of tryptophan resulting in decreased conversion of tryptophan to niacin genetics autosomal recessive prognosis episodes become less common with age generally normal lifespan Presentation Symptoms pellagra with onset in childhood consisting of diarrhea dementia dermatitis failure to thrive episodes triggered by infections or other stressors Physical exam red rash usually due to photosensitivity ataxia during episodes of pellagra Studies Serologies ↓ tryptophan Labs ↑ neutral amino acids in urine Differential Pellagra due to vitamin deficiency Malignant carcinoid syndrome Treatment Conservative high protein diet indication for prophylaxis of symptoms recommended diet after diagnosis nicotinic acid indication for acute episodes of pellagra (dermatitis and confusion primarily) rationale nicotinic acid is an important metabolite of tryptophan, a neutral amino acid nicotninc acid is a precursor to to the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) nicotinic acid supplementation can restore NAD and NADP levels Complications Complications neurologic degeneration if pellagra is not treated properly