From hepatosplenomegaly to genetic diagnosis: A case of congenital disorder of glycosylation type IIb due to mannosyl-oligosaccharide glucosidase mutation

Congenital disorders of glycosylation (CDG) are rare metabolic conditions with heterogeneous presentations, often complicating diagnosis. We report a 5-year-old male born to consanguineous parents, presenting with a 2-year history of painless abdominal distension, massive splenomegaly, and a stable popliteal spindle cell nodule. Growth parameters were subnormal (weight: −1.3 standard deviation [SD]; height: −2.1 SD), with laboratory findings revealing iron-deficiency anemia, thrombocytopenia, and hyperammonemia. Storage disorders, hematologic malignancies, and tropical causes were excluded from the study. Whole-exome sequencing identified a homozygous variant of uncertain significance in mannosyl-oligosaccharide glucosidase, confirming CDG type IIb (CDG2B). Notably, the popliteal spindle cell lesion, absent in prior CDG2B reports, expands the phenotypic spectrum of this ultra-rare disorder. The case underscores the diagnostic utility of genetic testing in consanguineous pediatric populations with unexplained hepatosplenomegaly and growth delays, particularly when traditional metabolic screens are inconclusive. While management remains supportive, early diagnosis enables surveillance for hepatic, hematologic, or immunologic complications. This report highlights CDG2B’s clinical variability and reinforces the role of next-generation sequencing in unravelling cryptic metabolic diagnoses.