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2025, Number 4

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Rev Mex Pediatr 2025; 92 (4)

Clinical and molecular spectrum of Imerslund-Gräsbeck syndrome

Bindi V, Crespo C, Eiroa H, Gravina LP, Rossetti E

Language: Spanish
References: 15
Page: 156-161
PDF size: 405.17 Kb.


ABSTRACT

Introduction: Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder caused by pathogenic variants in the CUBN or AMN genes, leading to malabsorption of vitamin B12 (cobalamin). Patients with IGS have anemia, gastrointestinal symptoms, and growth retardation. Description of cases: we present four Argentinian patients with IGS, whose clinical presentation was characterized by fatigue, pallor, neurodevelopmental delay, diarrhea, and vomiting. Three had megaloblastic anemia and one had macrocytic anemia. All had vitamin B12 deficiency (serum levels < 125 pg/mL), as well as persistent proteinuria. The median age of onset was 21 months, and the median age at diagnosis was nine years. A novel homozygous variant in CUBN (c.2450G>A; p.Cys817Tyr) was identified in three patients, while the fourth patient carried a homozygous intronic deletion in AMN (c.1006+34_1007-31del). The treatment was with parenteral or oral cobalamin, with progressive improvement. Conclusions: in patients with anemia and vitamin B12 deficiency, IGS should be considered as part of the differential diagnosis. The concomitant identification of proteinuria may aid in its detection.


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