Intracellular Cobalamin Defect in Early Infancy: A Cause of Hypotonia and Cytopenias Publisher

Summary: Can a rare B12-processing disorder be treated? A case report links an MMACHC mutation to cblC; vitamin therapy improved tests but did not cure it. #RareDisease #Genetics

Saeedi M ; Sangsari R ; Rostami P ; Mirnia K ; Shams S ; Rahmati S
Source: Case Reports in Medicine Published:2026

Abstract

Intracellular cobalamin metabolism defects (ICMDs) are rare but inherited disorders that disrupt the conversion of cobalamin into its active cofactors, methylcobalamin and adenosylcobalamin. We report a 40-day-old female infant with progressive hypotonia, poor feeding, hydrocephalus, and pancytopenia, whose metabolic profile demonstrated severe hyperhomocysteinemia, elevated urinary methylmalonic acid, and low methionine despite normal serum vitamin B12. Bone marrow evaluation revealed profound hypercellularity with megaloblastic changes and hypersegmented neutrophils. These findings suggested an intracellular cobalamin defect, most consistent with the cblC subtype. Molecular analysis confirmed a homozygous frameshift mutation in the MMACHC gene, establishing the diagnosis of methylmalonic aciduria and homocystinuria, cblC type. Treatment with hydroxocobalamin, betaine, and folinic acid led to stabilization of hematologic parameters and significant clinical and biochemical improvement; however, it is important to recognize that therapy is not curative, and long-term neurodevelopmental outcomes may remain guarded, especially in early-onset cases. Copyright © 2026 Maryam Saeedi et al. Case Reports in Medicine published by John Wiley & Sons Ltd.