Hartnup Disease Flashcards
A 10-year-old boy is brought to the clinic due to skin rash and difficulty walking. His mother notes that the rash worsens after sun exposure, and he has also been experiencing loose stools. Physical examination reveals erythematous, scaly plaques on sun-exposed areas and cerebellar ataxia. Laboratory findings include increased neutral amino acids in the urine. Which of the following is the most likely cause of this patient’s symptoms?
A) Defective absorption of neutral amino acids in the renal and intestinal epithelium
B) Deficiency of branched-chain alpha-ketoacid dehydrogenase
C) Impaired renal reabsorption of cystine and dibasic amino acids
D) Deficiency of phenylalanine hydroxylase
E) Defective metabolism of methionine
Answer: Defective absorption of neutral amino acids in the renal and intestinal epithelium
Explanation: Hartnup Disease is an autosomal recessive disorder caused by mutations in the SLC6A19 gene, which encodes a Na+-dependent transporter for neutral amino acids, including tryptophan. The defective transporter leads to decreased tryptophan absorption, resulting in reduced niacin synthesis and symptoms of vitamin B3 deficiency, such as pellagra (dermatitis, diarrhea, and dementia) and cerebellar ataxia. Neutral aminoaciduria (elevated neutral amino acids in the urine) is a hallmark finding. Treatment involves a high-protein diet to compensate for amino acid losses and niacin supplementation.
Incorrect Answers:
B) Deficiency of branched-chain alpha-ketoacid dehydrogenase causes maple syrup urine disease, characterized by sweet-smelling urine and neurologic symptoms.
C) Impaired renal reabsorption of cystine and dibasic amino acids occurs in cystinuria, leading to recurrent kidney stones, not niacin deficiency symptoms.
D) Deficiency of phenylalanine hydroxylase causes phenylketonuria (PKU), presenting with intellectual disability and musty body odor, not pellagra or ataxia.
E) Defective metabolism of methionine occurs in homocystinuria, characterized by marfanoid features and thromboembolism, not pellagra or ataxia.
What is the genetic inheritance pattern of Hartnup Disease?
Autosomal recessive
What is the underlying genetic mutation in Hartnup Disease?
Mutation in the SLC6A19 gene, encoding a Na+-dependent neutral amino acid transporter
What is the primary pathophysiology of Hartnup Disease?
Defective transport of neutral amino acids in the renal and intestinal epithelium, leading to decreased absorption of tryptophan
What amino acid is primarily affected in Hartnup Disease?
Tryptophan
What are the clinical features of Hartnup Disease?
Symptoms of vitamin B3 (niacin) deficiency: pellagra (dermatitis, diarrhea, dementia), glossitis, and cerebellar ataxia
What laboratory finding is characteristic of Hartnup Disease?
Increased neutral amino acids in the urine (neutral aminoaciduria)
What dietary modifications are recommended for managing Hartnup Disease?
High-protein diet to compensate for amino acid losses
What supplementation is beneficial in Hartnup Disease?
Niacin (vitamin B3) supplementation
