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

Kjærgaard, Susanne; Schwartz, Marianne; Skovby, Flemming

doi:10.1136/adc.85.3.236

Cited by 80 publications

(77 citation statements)

References 20 publications

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“…Therefore, a correlation between the F157S mutation and a severe neonatal phenotype might be possible. This hypothesis is further supported by homozygous cases of either D65Y or F119L presenting a less severe phenotype [7,9]. Finally, for a more detailed genotype phenotype correlation, more cases need to be collected and evaluated in a systematic manner.…”

Section: Discussionmentioning

confidence: 95%

Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema

Noelle

Knuepfer

Pulzer³

et al. 2005

Eur J Pediatr

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Section: Discussionmentioning

confidence: 95%

Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema

Noelle

Knuepfer

Pulzer³

et al. 2005

Eur J Pediatr

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“…CDG-Ia patients with the R141H/F119L genotype represent the severe end of the clinical spectrum. 6 Severe failure to thrive, severe psychomotor retardation, cerebellar atrophy, hypotonia, ataxia, polyneuropathy, hepatic dysfunction, inverted nipples, and abnormal subcutaneous fat pads are consistent features of this genotype.…”

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confidence: 94%

Ophthalmic manifestations of congenital disorder of glycosylation type 1a

Jensen¹,

Kjærgaard²,

Klie³

et al. 2003

Ophthalmic Genetics

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The present study illustrates the difficulties in examining severely disabled children. Consistent ophthalmic manifestations of CDG-Ia patients due to the R141H/F119L genotype were congenital esotropia, DVM, and a reduced rod response in ERG-examined patients. The vast majority of patients had reduced VA and developed myopia. We speculate that there is a relationship between the glycosylation defect in CDG-Ia and the development of myopia. We recommend that CDG-Ia patients be followed annually by an ophthalmologist.

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“…While there were differences in phenotypes within the group, 12 the anthropometric data showed remarkably similarity. Measurements of length, weight, and head circumference were within normal ranges at birth, but during the first seven months of life mean values of weight and length SDS declined dramatically.…”

Section: Discussionmentioning

confidence: 87%

Prepubertal growth in congenital disorder of glycosylation type Ia (CDG-Ia)

Kjærgaard

Müller²,

Skovby³

2002

Archives of Disease in Childhood

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Aims: To delineate the pattern of growth in prepubertal children with congenital disorder of glycosylation type Ia (CDG-Ia) in order to identify critical period(s) and possible cause(s) of growth failure. Methods: Longitudinal measurements of weight, length/height, and head circumference from birth to 10 years of age in 25 CDG-Ia patients with the R141H/F119L PMM2 genotype were analysed. The data and derived body mass indices (BMI) were compared with standards and expressed as standard deviation scores (SDS). A linear mixed effects model was fitted to each set of data, and mean curves were estimated. Results: The mean weight SDS decreased from −0.3 at birth to −3.0 at 7 months of age and remained low or increased slightly. The mean length SDS decreased from zero at birth to −2.4 at 7 months of age followed by a slight increase to a maximum of −1.8 SDS at the end of the second year of life. After age 2 the mean length/height SDS decreased again. The mean BMI SDS at birth was −0.7 and declined to a minimum of −2.8 at the end of the second year of life followed by a gradual increase. The mean head circumference SDS declined gradually from 0 at 3 months of age to −1.9 at age 5. Conclusion: CDG-Ia patients with the R141H/F119L genotype have normal fetal growth and an immediate postnatal onset of severe growth failure. A notable decline in weight end length SDS takes place during the first seven months of life with no prepubertal catch up. C ongenital disorders of glycosylation (CDG), formerly known as carbohydrate deficient glycoprotein syndromes, are a rapidly growing group of disorders resulting from defects in the carbohydrate side chain (glycans) of proteins. The importance of glycans for the structure, function, and metabolism of glycoproteins is reflected by the severity of multisystem diseases resulting from defective N-glycan synthesis.Congenital disorder of glycosylation type Ia (CDG-Ia, OMIM 212065), by far the most common type, is caused by deficiency of phosphomannomutase, an enzyme that converts mannose-6-phosphate to mannose-1-phosphate.1 As a consequence the pool of GDP-mannose, which acts as a donor of mannose, is significantly reduced and leads to hypoglycosylation of proteins.Phosphomannomutase is encoded by the PMM2 gene, and CDG-Ia is inherited as an autosomal recessive trait.2 In a recent mutation update, compound heterozygosity for the R141H and the F119L mutation was the most frequent genotype, accounting for 27% of 249 patients from 23 countries. Failure to thrive is a prominent feature, although its reported onset and degree have been variable. [4][5][6] We have analysed longitudinal data of weight, length/height, and head circumference in our 25 patients with the R141H/F119L genotype in order to delineate the prepubertal growth pattern and to identify critical period(s) and possible cause(s) of growth failure. PATIENTS AND METHODS PatientsThe 25 CDG-Ia patients (13 girls and 12 boys; mean age 7.6 years, range 0-19) with the R141H/F119L PMM2 genotype came from 19 unrelated families of Danish...

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

Cited by 80 publications

References 20 publications

Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema

Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema

Ophthalmic manifestations of congenital disorder of glycosylation type 1a

Prepubertal growth in congenital disorder of glycosylation type Ia (CDG-Ia)

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