Thiamine-Responsive Megaloblastic Anemia Syndrome

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia, progressive sensorineural hearing loss, and diabetes mellitus. Onset of megaloblastic anemia occurs between infancy and adolescence. The anemia is corrected with thiamine treatment, but the red cells remain macrocytic and anemia can recur if treatment is withdrawn. Progressive sensorineural hearing loss often occurs early and can be detected in toddlers; hearing loss is irreversible and may not be prevented by thiamine treatment. The diabetes mellitus is non-type I in nature, with age of onset from infancy to adolescence. Thiamine treatment may reduce insulin requirement and delay onset of diabetes in some individuals.

Diagnosis/testing: The diagnosis of TRMA is established in a proband with: megaloblastic anemia with normal vitamin B12 / folic acid levels, with or without diabetes or hearing loss, in whom there is a response to oral thiamine; and/or biallelic pathogenic variants in SLC19A2 identified by molecular genetic testing.

Management: Treatment of manifestations: Lifelong use of pharmacologic doses (50-100 mg/day) of oral thiamine (vitamin B1) in affected individuals regardless of age. Red blood cell transfusion for severe anemia. Standard treatment for sensorineural hearing loss, diabetes mellitus, and ophthalmologic, cardiovascular, and neurologic manifestations.

Surveillance: At least annual monitoring of the efficacy of the oral thiamine therapy and of disease progression, including: hematologic tests (CBC, reticulocyte count); assessment for glucose intolerance (fasting serum glucose concentration, oral glucose tolerance test, urinalysis); and hearing, ophthalmologic, cardiac, and neurologic evaluations.

Pregnancy management: Good diabetic control prior to and during pregnancy is recommended.

Genetic counseling: TRMA is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible for families in which the SLC19A2 pathogenic variants have been identified in the affected family member.

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