Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrumof the R141H/F119L genotype

Aims-To delineate common and variable features and outcome of children with congenital disorder of glycosylation type Ia (CDG-Ia) caused by the freque nt R141H/F119L PMM2 genotype. Methods-Clinical data on 25 patients (mean age 7.6 years, range 0-19) were analysed. Results-All patients had an early presentation with severe feeding problems and failure to thrive, hypotonia, hepatic dysfunction, inverted nipples, a nd abnormal subcutaneous fat pads. Eighteen patients were hospitalised in t he neonatal period. Developmental delay was obvious before age 6 months. Du ring the first seven months mean standard deviation score (SDS) for weight and length decreased 2.7 (SD = 2) and 2.4 (SD = 2), respectively. Mental re tardation, ataxia, muscular atrophy, and febrile seizures were consistent f eatures after infancy. Variable features included pericardial effusions, af ebrile seizures, and stroke like episodes. Computed tomography/magnetic res onance imaging of the brain was normal in two patients examined before 4 mo nths of age, but 18 children examined after 3 months of age had cerebellar atrophy, and 10 children also had supratentorial atrophy. Subsequent imagin g showed progression of the cerebellar and supratentorial atrophy in eight and four of 10 children, respectively. Mean head circumference SDS declined from zero to -1.9 SD from age 3 months to 5 years. Motor ability ranged fr om none to walking with a rolator, and vocabulary ranged from none to compr ehensible speech. The overall mortality ascribed to CDG-Ia was 18%. Conclusion-Patients with the R141H/F119L genotype have an early uniform pre sentation including severe failure to thrive, but their functional outcome is variable. This genotype may well cause clinical manifestations in the se vere end of the spectrum of CDG-Ia.