A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations

Abstract

<p>Abstract</p> <p>Background</p> <p>SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in <it>SLC19A3 </it>cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke's-like encephalopathy. Biotin and/or thiamin are effective therapies for both diseases.</p> <p>Methods</p> <p>We conducted on the detailed clinical, brain MRI and molecular genetic analysis of four Japanese patients in a Japanese pedigree who presented with epileptic spasms in early infancy, severe psychomotor retardation, and characteristic brain MRI findings of progressive brain atrophy and bilateral thalami and basal ganglia lesions.</p> <p>Results</p> <p>Genome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene <it>SLC19A3</it>. A pathogenic homozygous mutation (c.958G > C, [p.E320Q]) in <it>SLC19A3 </it>was identified in all four patients and their parents were heterozygous for the mutation. Administration of a high dose of biotin for one year improved neither the neurological symptoms nor the brain MRI findings in one patient.</p> <p>Conclusion</p> <p>Our cases broaden the phenotypic spectrum of disorders associated with <it>SLC19A3 </it>mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.</p