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Open Access Highly Accessed Research article

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

Kenichiro Yamada1, Kiyokuni Miura2, Kenju Hara3, Motomasa Suzuki2, Keiko Nakanishi4, Toshiyuki Kumagai2, Naoko Ishihara1, Yasukazu Yamada1, Ryozo Kuwano5, Shoji Tsuji6 and Nobuaki Wakamatsu1*

Author Affiliations

1 Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan

2 Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Aichi, Japan

3 Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan

4 Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan

5 Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan

6 Department of Neurology, University of Tokyo, Tokyo, Japan

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BMC Medical Genetics 2010, 11:171  doi:10.1186/1471-2350-11-171

Published: 22 December 2010

Abstract

Background

SLC19A3 (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.

Methods

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.

Results

Genome-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.

Conclusion

Our 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.