Clinical and Laboratory Observations
Carbohydrate-deficient glycoprotein syndrome type 1a: A variant phenotype with borderline cognitive dysfunction, cerebellar hypoplasia, and coagulation disturbances

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Abstract

An 8-year-old boy is described with borderline cognitive impairment, cerebellar hypoplasia, a stroke-like episode, and venous thrombosis of the left leg after a period of immobilization. The pattern of multiple abnormalities in blood coagulation suggested carbohydrate-deficient glycoprotein syndrome type 1a. Isoelectric focusing of serum transferrin was abnormal. The activity of phosphomannomutase in leukocytes and fibroblasts was decreased. Mutation analysis of the PMM2 gene revealed the R141H/E151G genotype. These results confirm the presence of carbohydrate-deficient glycoprotein syndrome type 1a without severe psychomotor retardation. (J Pediatr 2000;136:400-3)

Section snippets

CASE REPORT

The patient is an 8-year-old son of non-consanguineous white parents, born at term after a normal pregnancy. His birth weight was 3250 g. No dysmorphism was observed, especially no inverted nipples and no fat pads. Length growth followed the 50th percentile, and weight evolution was between the 3rd and 10th percentiles. Examination at 9 months revealed bilateral convergent strabismus with intact range of eye movements on lateral rotation, spasmus nutans, hand dysmetria, and titubation. Cranial

DISCUSSION

Since the first report of a patient with CDG syndrome type 1a by Jaeken et al,1 about 200 patients have been identified. The clinical presentation of CDG syndrome type 1a is characterized by severe neurologic abnormalities, dysmorphism, and variable involvement of other organs.11, 12 The neurologic features are age-related. Hypotonia, muscular weakness, developmental retardation, and alternating esotropia and hyporeflexia can be observed in the neonatal and infantile periods. After infancy,

Acknowledgements

We thank G. Matthijs and J. J. Cassiman from the Centre for Human Genetics in Leuven for the mutation screening in the PMM2 gene, C. Dekker from the Laboratory of Genetic Metabolic Diseases in Amsterdam for determination of the residual activity of PMM in fibroblasts, and I. Postma from the Department of Psychology of Emma Children’s Hospital AMC for performing the Wechsler Intelligence Scale for Children-Revised test in the patient.

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    Reprint requests: C. H. van Ommen, MD, Academic Medical Centre/University of Amsterdam, Emma Children’s Hospital AMC/Department of Pediatric Hematology, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.

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