Hartnup disease is an autosomal recessive condition characterized by neutral aminoaciduria and behavioral problems. It is caused by a loss of B0AT1, a neutral amino acid transporter in the kidney and intestine. CLTRN encodes the protein collectrin that functions in the transportation and activation of B0AT1 in the renal apical brush bordered epithelium. Collectrin deficient mice have severe aminoaciduria. However, the phenotype associated with collectrin deficiency in humans has not been reported. Here we report two patients, an 11-year-old male who is hemizygous for a small, interstitial deletion on Xp22.2 that encompasses CLTRN and a 22-year-old male with a deletion spanning exons 1 to 3 of CLTRN. Both of them present with neuropsychiatric phenotypes including autistic features, anxiety, depression, compulsions, and motor tics, as well as neutral aminoaciduria leading to a clinical diagnosis of Hartnup disease and treatment with niacin supplementation. Plasma amino acids were normal in both patients. One patient had low 5-hydroxyindoleacetic acid levels, a serotoninergic metabolite. We explored the expression of collectrin in the murine brain and found it to be particularly abundant in the hippocampus, brainstem, and cerebellum. We propose that collectrin deficiency in humans can be associated with aminoaciduria and a clinical picture similar to that seen in Hartnup disease. Further studies are needed to explore the role of collectrin deficiency in the neurological phenotypes.
|Original language||English (US)|
|Number of pages||10|
|Journal||American Journal of Medical Genetics, Part A|
|State||Published - Dec 1 2019|
Bibliographical noteFunding Information:
This work was funded in part by a Sanofi Genzyme ACMGF Next Generation Training Award to NRP and a National Institutes of Health grant (T32 GM07526-41) to BJS, and by the Departament de Salut de la Generalitat de Catalunya (PERIS SLT002/16/00174) to FP. AGC is funded by FIS: PI15/01082 and PI18/0111 (Instituto de Salud Carlos III: ISCIII and Fondo Europeo de desarrollo regional, FEDER).
© 2019 Wiley Periodicals, Inc.
- Hartnup disease