Thiamine responsive megaloblastic anemia: the puzzling phenotype.

Area of Science:

• Genetics
• Pediatrics
• Hematology

Background:

• Thiamine responsive megaloblastic anemia (TRMA) is a rare genetic disorder.
• It is characterized by megaloblastic anemia, non-type 1 diabetes mellitus, and sensorineural deafness.
• The SLC19A2 gene is implicated in TRMA.

Purpose of the Study:

• To investigate the clinical manifestations of Omani children diagnosed with TRMA.
• To determine the genotype-phenotype relationship in these patients.

Main Methods:

• Retrospective collection of clinical and laboratory data from Omani patients.
• Mutation analysis using microsatellite markers and fluorescent-labeled PCR primers.
• PCR amplification to define deletion breakpoint regions in the SLC19A2 gene.

Main Results:

• Six Omani children (5 female, 1 male) were diagnosed with TRMA.
• All presented with sensorineural deafness at birth; anemia onset varied.
• A novel 5,224 bp deletion in SLC19A2 involving exons 4-6 was found in all patients.
• One patient exhibited a rare Uhl cardiac anomaly, previously undescribed in TRMA.

Conclusions:

• TRMA exhibits an expanding phenotypic spectrum.
• The study found a poor genotype-phenotype correlation in the investigated Omani cohort.