Thiamine-responsive megaloblastic anemia syndrome (TRMA)
Incidence
Autosomal recessive.
Clinical Characteristics
Bazarbachi et al. (1998) found reports of 15 patients with the triad of thiamine-responsive anemia, diabetes mellitus, and deafness associated with macrocytic anemia and sometimes moderate thrombocytopenia. Bone marrow aspirates usually showed ringed sideroblasts in addition to the megaloblastic changes. They described 2 new patients who presented with diabetes, deafness, and thiamine-responsive pancytopenia. Bone marrow aspirate and biopsy were typical of trilineage myelodysplasia. The findings suggested that thiamine may have a role in the regulation of hemopoiesis at the stem cell level. They proposed the designation 'thiamine-responsive myelodysplasia' for this disorder. Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia, diabetes mellitus, and sensorineural hearing loss. Megaloblastic anemia occurs between infancy and adolescence. The anemia is corrected with pharmacologic doses of thiamine (vitamin B1) (25-75 mg/day compared to US RDA of 1.5 mg/day). However, the red cells remain macrocytic. The anemia can recur when thiamine is withdrawn. The diabetes mellitus is non-type I in nature, with age of onset from infancy to adolescence. Progressive sensorineural hearing loss is irreversible and may not be prevented by thiamine treatment. The diagnosis of TRMA is based on the triad of clinical features described above. Examination of the bone marrow reveals megaloblastic anemia with erythroblasts often containing iron-filled mitochondria (ringed sideroblasts). SLC19A2, which encodes the high-affinity thiamine transporter, is the only gene known to be associated with TRMA. All patients with the diagnostic phenotypic triad evaluated by sequence analysis have identifiable mutations in the SLC19A2 gene.
Precipitants
Withdrawal from thiamine
Provocation Tests
Withdrawal from thiamine probable.
Diagnostic Procedures
The diagnosis of TRMA is based on the triad of clinical features described above. Examination of the bone marrow reveals megaloblastic anemia with erythroblasts often containing iron-filled mitochondria (ringed sideroblasts). SLC19A2, which encodes the high-affinity thiamine transporter, is the only gene known to be associated with TRMA. All patients with the diagnostic phenotypic triad evaluated by sequence analysis have identifiable mutations in the SLC19A2 gene.