SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.
Four patients, aged 7-20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present patients' phenotype is markedly different, with normal head circumference, normal early childhood development, age-appropriate cognitive skills, and normal urinary organic acid profile. Determination of the SLC25A19 sequence should be considered in patients with bilateral striatal necrosis and progressive polyneuropathy.
Spiegel
Ronen
R
Department of Human Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Shaag
Avraham
A
Edvardson
Simon
S
Mandel
Hanna
H
Stepensky
Polina
P
Shalev
Stavit A
SA
Horovitz
Yoseph
Y
Pines
Ophry
O
Elpeleg
Orly
O
D000293:Adolescent; D000328:Adult; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002648:Child; D003342:Corpus Striatum / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D009336:Necrosis / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D011115:Polyneuropathies / Q000235:genetics*
D004272:DNA, Mitochondrial; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; C434255:SLC25A19 protein, human