A novel homozygous nonsense mutation (p.Y78*) in TMPRSS6 gene causing iron-refractory iron deficiency anemia (IRIDA) in two siblings

Abstract

Iron-refractory iron deficiency anemia (IRIDA) is an inherited iron metabolism disorder caused by mutations in TMPRSS6 gene encoding matriptase-2, which results in increased hepcidin synthesis. The hallmarks of the disease are hypochromic microcytic anemia, low transferrin saturation, slightly low or normal ferritin levels in contrast to classic iron deficiency anemia (IDA), inadequate response to oral iron, and only a partial response to parenteral iron. We report here a 6-year-old Syrian boy with unexplained microcytic anemia since one year of age. Genetic analysis of the TMPRSS6 gene revealed a novel homozygous nonsense mutation in exon 3 (c.234C>G; p.Y78* or p.Tyr78*). In the presence of hypochromic microcytic anemia accompanied by atypical iron parameters not in accordance with classic IDA, and inadequate response to iron therapy, IRIDA should be remembered in the differential diagnosis.

Response to Prolonged Duration of Therapeutic Dose Oral Iron Therapy in a Girl With Novel TMPRSS6 Gene Variants: A Case Report and Review Literature

“…The youngest age group was reported in the infancy period 17,20,23,25,29,32,34,35,38,40,43. The median (range) of hepcidin and hemoglobin levels were 57.1 (2.5 to 6,292.5 nmol/L) or 157.7 (6.9 to 17,382.6 ng/mL), and 8.2 (4.4 to 13.9) g/dL, respectively 13–43. When the data were collated, there was a correlation between hemoglobin and hepcidin levels ( r =0.24, P =0.034).…”

“…(Table 1) Most of the reported patients presented in the childhood period, either symptomatic or incidental, with few exceptions. The youngest age group was reported in the infancy period 17,20,23,25,29,32,34,35,38,40,43. The median (range) of hepcidin and hemoglobin levels were 57.1 (2.5 to 6,292.5 nmol/L) or 157.7 (6.9 to 17,382.6 ng/mL), and 8.2 (4.4 to 13.9) g/dL, respectively 13–43.…”