Congenital disorder of glycosylation type 1a in a macrosomic 16-month-old boy with an atypical phenotype and homozygosity of the N216I mutation.

UNLABELLED: We report on a 16-month-old boy with congenital disorder of glycosylation type 1a (CDG-1a; OMIM 212065) showing an atypical phenotype. Whereas failure to thrive is known to be a prominent feature in this condition, our patient developed postnatal macrosomia with increase of weight, length and occipitofrontal circumference (OFC) above the 95th percentile within his 1st year of life. Thereafter, weight and length were close to the 90th and OFC at the 50th percentiles. In contrast to other CDG-1a patients, the child did not have abnormal fat pads or inverted nipples; but unusual eyebrows were present. CDG-1a was confirmed by isoelectric focusing of serum transferrin and measurement of phosphomannomutase activity in leucocytes and cultured fibroblasts (residual activity <5% of controls). Mutation analysis of the phosphomannomutase 2 gene (PMM2) revealed homozygosity for a 647A>T (N216I) mutation in our patient and heterozygosity in his consanguineous parents.
CONCLUSION: This is the first report of macrosomia and of homozygosity for the 647A>T (N216I) mutation in a patient with congenital disorder of glycosylation type 1a which may allow further phenotype/genotype comparisons.