CONGENITAL DISORDER OF GLYCOSYLATION TYPE I-A

Congenital disorder of glycosylation type Ia (CDG-Ia) is caused by a defect in the synthesis of N-glycans due to mutations in the PMM2 gene encoding phosphomannomutase 2. The aim of the study was to analyse the clinical course of the disease in 15 children with CDG-Ia diagnosed on biochemical and/or molecular level. Results All patients had early onset of the disease with failure to thrive, hypotonia, strabismus and coagulopathy. Majority of them had inverted nipples and atypical fat pads (86%, 77% respective). Mental retardation, ataxia, microcephaly and polyneuropathy were consistent features after infancy. Stroke-like episodes were observed in 27% of patients. All but one patient developed visual impairment with retinitis pigmentosa in half of them. Hepatosplenomegaly was present in 60% and hepatopathy in 80% of examined children. Two patients manifested with liver failure, in one of them liver fibrosis was recognised at autopsy. Ultrasonography of kidney revealed multiple microcysts formation with poor corticomedullar distinction in two patients and hydronephrosis in one. Cardiomyopathy and/or pericardial effusion were observed in three children. Non-immune hydrops foetalis was diagnosed in one patient. Conclusion The clinical presentation in children with CDG type Ia ranges from moderate neurological symptoms to severe multi-organ failure. All children presented with severe chronic neurological manifestations combined with extraneurological involvement of various tissues including liver and kidney. In addition, a combination of several factors including coagulopathy, thrombocytopathy, acute febrile infection and haemoconcentration contributed to the development of stroke-like phenomena in four of our patients. Supported by IGA 8320-4 and MSM 0021620806.