Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrum of the R141H/F119L genotype.
OBJECTIVE
To delineate common and variable features and outcome of children with congenital disorder of glycosylation type Ia (CDG-Ia) caused by the frequent 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, and abnormal subcutaneous fat pads. Eighteen patients were hospitalised in the neonatal period. Developmental delay was obvious before age 6 months. During 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 retardation, ataxia, muscular atrophy, and febrile seizures were consistent features after infancy. Variable features included pericardial effusions, afebrile seizures, and stroke like episodes. Computed tomography/magnetic resonance imaging of the brain was normal in two patients examined before 4 months of age, but 18 children examined after 3 months of age had cerebellar atrophy, and 10 children also had supratentorial atrophy. Subsequent imaging 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 from none to walking with a rolator, and vocabulary ranged from none to comprehensible speech. The overall mortality ascribed to CDG-Ia was 18%.


CONCLUSIONS
Patients with the R141H/F119L genotype have an early uniform presentation including severe failure to thrive, but their functional outcome is variable. This genotype may well cause clinical manifestations in the severe end of the spectrum of CDG-Ia.
Kjaergaard
S
S
Department of Clinical Genetics, University Hospital, Rigshospitalet 4062, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Susanne@rh.dk
Schwartz
M
M
Skovby
F
F
D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000235:genetics / Q000378:metabolism; D001284:Atrophy / Q000235:genetics / Q000378:metabolism; D002508:Cephalometry; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000235:genetics* / Q000378:metabolism; D002658:Developmental Disabilities / Q000235:genetics / Q000378:metabolism; D019066:Facies; D005183:Failure to Thrive / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006031:Glycosylation; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008111:Liver Function Tests; D008297:Male; D010641:Phenotype; D011379:Prognosis; D012640:Seizures / Q000235:genetics / Q000378:metabolism