title: A case of cystinuria presenting with cerebellar ataxia and dementia.
abstract: Cystinuria normally manifests as recurrent urinary stones and renal dysfunction, but can present to neurologists with ataxia, posterior column impairment, intellectual deficiency and pyramidal and extrapyramidal signs; the neuroradiological features include cerebellar, brainstem and cerebral atrophy. It is an autosomal recessive disease caused by a transport disorder of cystine and dibasic amino acids in renal proximal tubules. Most cases have an SLC3A1 and/or SLC7A9 gene mutation but some recent Japanese patients have had distinct heterozygous gene mutations. We report a patient with cystinuria with a heterozygous P482L mutation in the SLC7A9 gene, presenting with atrophy in the cerebellum, brainstem and cerebrum and with no urinary stones. Cystine, an amino acid comprising two cysteine molecules, is transported into cells via a cystine transporter. It is essential for producing hydrogen sulfate and the cellular antioxidant glutathione: these exert neuroprotection in astrocytes and cerebellar Purkinje cells. Although cystinuria is a metabolic disorder associated with renal dysfunction, we suspect that a trafficking defect of transporter rBAT-BAT1 in brain might cause neuronal degeneration, leading to cerebellar and cerebral atrophy.
authors.affiliation: Department of Neurology, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Tohge
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Department of Neurology, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D002524:Cerebellar Ataxia / Q000150:complications* / Q000235:genetics; D003555:Cystinuria / Q000150:complications*; D003704:Dementia / Q000150:complications* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D026923:Amino Acid Transport Systems, Basic; C499489:SLC7A9 protein, human
keywords: <i>SLC7A9</i>; CEREBELLAR ATAXIA; cerebral atrophy; cystinuria; heterozygous P482L mutation