Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thiamine transporter gene SLC19A2 was recently found to be mutated in thiamine responsive megaloblastic anaemia with diabetes and deafness (TRMA, Rogers syndrome), an early onset autosomal recessive disorder. We now report a novel G1074A transition mutation in exon 4 of the SLC19A2 gene, predicting a Trp358 to ter change, in a girl with consanguineous parents. In addition to the typical triad of Rogers syndrome, the girl presented with short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Both muscle and skin biopsies were obtained before high dose thiamine supplementation. While no mitochondrial abnormalities were seen on morphological examination of muscle, biochemical analysis showed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. In the patient's fibroblasts, the supplementation with high doses of thiamine resulted in restoration of complex I activity. In conclusion, we provide evidence that thiamine deficiency affects complex I activity. The clinical features of TRMA, resembling in part those found in typical mitochondrial disorders with complex I deficiency, may be caused by a secondary defect in mitochondrial energy production.
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PMID:A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. 1097 58

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive disorder characterized by diabetes mellitus (DM), progressive sensorineural deafness, and thiamine-responsive anemia. Mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter protein THTR-1 are responsible for the clinical features associated with TRMA syndrome. We report an African-American female with TRMA-syndrome associated with thyroid disease and retinitis pigmentosa caused by a novel mutation in the SLC19A2 gene. The patient presented at 12 months of age with paroxysmal atrial tachycardia and hepatosplenomegaly. One month later, she developed DM requiring intermittent insulin therapy. At 2-1/2 years of age, profound sensorineural hearing loss was discovered. By 4 years of age, daily insulin therapy (0.5 U/kg/day) was instituted and her insulin requirement gradually increased to 1.0 U/kg/day by 9 years of age. She developed optic atrophy, retinitis pigmentosa, and visual impairment by 12 years of age with severe restriction of peripheral vision by 16 years. At age 19, a thiamine-responsive normocytic anemia was discovered. She was diagnosed with autoimmune thyroiditis at 20 years and she experienced a psychotic episode associated with a mood disorder at age 21. With oral thiamine therapy, her insulin requirement decreased by 30% over a 20 month period. Molecular analysis revealed that the patient is homozygous for a missense mutation (C152T) in exon 1 of the SLC19A2 gene.
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PMID:Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome. 1499 41