Am J Case Rep. 2025 Nov 3;26:e948797. doi: 10.12659/AJCR.948797.
ABSTRACT
BACKGROUND Congenital disorders of glycosylation (CDG) are rare, inherited metabolic conditions caused by defects in glycoprotein synthesis. CDG Type 1T, associated with mutations in the phosphoglucomutase 1 (PGM1) gene, often presents with hepatic dysfunction, developmental delay, and multisystem involvement. Due to clinical overlap with other metabolic disorders, misdiagnosis is common, leading to delayed treatment. CASE REPORT We report a 20-month-old boy, born to consanguineous parents, who initially received a misdiagnosis of galactosemia following abnormal newborn screening. Despite dietary modifications, he developed persistent transaminitis, coagulopathy, hypotonia, and delayed motor milestones. Further evaluation revealed abnormal carbohydrate-deficient transferrin analysis, and whole exome sequencing identified a homozygous PGM1 variant of uncertain significance, supporting CDG Type 1T diagnosis. Liver biopsy demonstrated steatosis with bridging portal fibrosis. The patient was started on oral D-galactose supplementation (1.5 g/kg/day). Over a 51-day follow-up period, liver enzymes improved markedly, with AST declining from 1980 to 385 U/L and ALT from 695 to 210 U/L, alongside normalization of coagulation profiles. Muscle enzyme response was partial, with creatine kinase levels remaining mildly elevated, reflecting differential therapeutic effects across tissues. CONCLUSIONS This case underscores the diagnostic challenges of CDG Type 1T and emphasizes the importance of combining biochemical markers and genetic sequencing to achieve timely diagnosis. The identified PGM1 variant, although classified as a variant of uncertain significance, was strongly supported by clinical and biochemical findings. Significant hepatic improvement with D-galactose highlights the therapeutic potential of early targeted supplementation, although incomplete muscular response indicates the need for ongoing follow-up and exploration of adjunctive therapies.
PMID:41182978 | DOI:10.12659/AJCR.948797
