Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Hartnup disease is an autosomal recessive condition characterized by neutral aminoaciduria and behavioral problems. It is caused by a loss of B<jats:sup>0</jats:sup>AT1, a neutral amino acid transporter in the kidney and intestine. <jats:italic>CLTRN</jats:italic> encodes the protein collectrin that functions in the transportation and activation of B<jats:sup>0</jats:sup>AT1 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 <jats:italic>CLTRN</jats:italic> and a 22‐year‐old male with a deletion spanning exons 1 to 3 of <jats:italic>CLTRN</jats:italic>. 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.</jats:p>