New aspects for the brain in Hartnup disease based on mining of high-resolution cellular mRNA expression data for SLC6A19

Hartnup disease is an autosomal recessive, metabolic disorder caused by mutations of the neutral amino acid transporter, SLC6A19/B0AT1. Reduced absorption in the intestine and kidney results in deficiencies in neutral amino acids and their down-stream metabolites, including niacin, associated with skin lesions and neurological symptoms. The effects on the nervous system such as ataxia have been related to systemic deficiencies of tryptophan (and other neutral amino acids) as no expression of the B0AT1 transporter was found in the brain. In the intestine, SLC6A19 cooperates with ACE2 which has received major attention as the cellular receptor for SARS-CoV-2. When transcriptomics data for ACE2 and its partner proteins were examined, a previously unrecognized expression of Slc6a19 mRNA in the ependymal cells of the mouse brain was encountered that is set into the context of neurological manifestations of Hartnup disease with this communication. A novel role for SLC6A19/B0AT1 in amino acid transport from CSF into ependymal cells is proposed and a role of niacin in ependymal cells highlighted. •Mutations of the neutral amino acid transporter, SLC6A19/B0AT1, cause Hartnup disease.•Hartnup disease is associated with various neurological symptoms due to systemic deficiencies of neutral amino acids and their metabolites.•In intestinal cells, ACE2 serves as physiological partner for SLC6A19/B0AT1.•Research on ACE2 as coronavirus receptor lead to transcriptomics level evidence for SLC6A19 expression mouse ependymal cells.•Deficiency of SLC6A19/B0AT1 in the brain may in part be causing neurological symptoms in Hartnup disease.