A wide spectrum of clinical and brain MRI findings in patients with SLC19A3mutations

Abstract

BackgroundSLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 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.MethodsWe 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.ResultsGenome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene SLC19A3. A pathogenic homozygous mutation (c.958G > C, [p.E320Q]) in SLC19A3 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.ConclusionOur cases broaden the phenotypic spectrum of disorders associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.

Biotin-Responsive Basal Ganglia Disease: Neuroimaging Features before and after Treatment

“…Subsequent reports confirmed these findings and added the involvement of the thalami, cerebellum, and brain stem. 2,5 Our results supported the findings of these previous reports regarding the MR imaging distribution of lesions in all cases. In addition, the globus pallidi were spared in all patients in agreement with most of previous reports.…”

Neuropathological characteristics of the brain in two patients with SLC19A3 mutations related to the biotin-thiamine-responsive basal ganglia disease

“…Although in the literature there are numerous magnetic resonance imagining (MRI) series of SLC19A3 defect illustrating both specific changes in detail [6,17] and the response to specific treatment [1,2], only few reports focus on brain pathology in affected patients [15]. Herein, we present our unique autopsy findings ("walnut" appearance of the brain) in a Polish child who died many years ago, and in whom the underlying SLC19A3 homozygous mutation has been recently established by WES (whole-exome sequencing).…”

Detection of Genomic Imbalances by Array-Based Comparative Genomic Hybridization in Bulgarian Patients with Autism Spectrum Disorders

“…no data has been reported on the relation between MFF mutations and autism, but it is well known that mitochondrial dysfunction can lead to ASDs (33). homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke's-like encephalopathy (43). TM4SF20 and WDR69 are expressed in the central nervous system, however their functions have not been well investigated.…”