OBJECTIVES: A 10-year-old boy presented with cleft palate, hepatopathy, cholecystolithiasis, myopathy, coagulopathy, hyperlipidemia, hypoglycemia, hyperuricemia, short stature, obesity, hypothyroidism, microcephaly and mild intellectual disability. The multi-systemic manifestation involving certain distinct clinical features prompted us to search for a subtype of congenital disorders of glycosylation (CDG). METHODS: The patient was screened for CDG by examining the distribution of transferrin (TRF) and apolipoprotein C-III (ApoC-III) sialylated isoforms using isoelectric focusing of serum. This was followed by spectrophotometric measurement of phosphoglucomutase 1 (PGM1) activity in fibroblasts and molecular analysis including sequencing and PCR-RFLP of PGM1 gene. Selected bioinformatics tools were used to evaluate the data. RESULTS: Increased relative levels of di-, mono- and asialotransferrin reflected a defect of N-glycosylation in the patient. Markedly decreased activity of PGM1 corresponding to less than 5% of control´s was found. Sequencing of PGM1 gene revealed the presence of two heterozygous missense mutations c.1010C>T (p.T337M) and c.1508G>A (p.R503Q), whose pathogenicity was confirmed by in silico analysis. CONCLUSION: We report the first Czech patient with a glycosylation disorder due to PGM1 deficiency. Compared to the described cases, no dilated cardiomyopathy was noted in our patient. However, he suffered from a mild neurological impairment, which is an uncommon feature that extends the phenotype associated with PGM1-CDG. Lactose-rich diet, which was previously reported to have ameliorated the clinical symptoms in some PGM1-CDG patients, did not result in any improvement in our patient.

Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic