CDG: a new case of a combined defect in the biosynthesis of N- and O-glycans

Abstract

We report on a 5.5-year-old boy with a multiple malformation syndrome and biochemical abnormalities suggesting a combined defect in the biosynthesis of Nand O-glycans. The patient was followed prenatally for intrauterine growth retardation and a finding of intestinal obstruction (double bubble sign). Born full term as the first child of healthy, non-related Czech parents without remarkable family history, his Apgar scores were 6, 6, and 7; birth weight 2,310 g; body length 45 cm; and head circumference 32.5 cm. He presented with dysmorphic features, including dolichocephaly, low hairline, high nasal bridge, thin lips, small chin, gothic palate, blepharophimosis and epicanthus, in addition to other malformations, such as arachnodactyly, unusual palmar creases, sinus sacralis, pes equinovarus, hypospadias, inguinal hernia, cryptorchidism, vesicoureteral reflux, peripheral pulmonary stenosis, and patent foramen ovale. Shortly after birth a surgical correction of intestinal malrotation and duodenal stenosis (Ladd’s syndrome) was done. Neonatal brain ultrasonography, ophthalmologic examination, a skeletal survey and an electrocardiogram were normal. Chromosome analysis was normal. Laboratory tests including serum lactate, ammonia, and immunological investigations were within normal limits. Serum biotinidase, plasma and urinary amino acids, organic acids, purines and pyrimidines, sugars, oligoand mucopolysaccharides did not reveal any pathological changes. At age 4 months, the brain ultrasonography showed hypogenesis of the posterior part of the corpus callosum (later confirmed by MRI), and abnormal EEG delta waves were noted occipitally, without epilepsy. In addition to anemia (90 g/l, normal 105–135), elevated LDH (12.7 μkat/l, normal< 4.4) and elevated transaminases (1.1–2.2 μmol/l, normal<0.8), prolonged values of APTT (39.3–45.6, normal range 31.8–35.0) and PT (13.3, normal 11.7) were found; antithrombin III and CK were within the physiological range. At 3.5 years, the boy was admitted to hospital with severe laryngopharyngitis, and at that time a screening for congenital disorders of glycosylation (CDG) was performed. Isoelectric focusing (IEF) and HPLC of serum transferrin (Tf) showed a slight increase in asialo-Tf (4.0%; reference interval, 0.0–3.0%), a marked increase in disialoTf (18.7%; reference interval, 2.5–9.8%), increased trisialo-Tf (17.8%; reference interval, 3.4–13.7%) and decreased tetrasialo-Tf (38.8%; reference interval, 43.7– 68.1%). Abnormalities of alpha1-antitrypsin (aAT) and thyroxin-binding globulin pointed to a generalised defect Z. Albahri . E. Marklova . P. Dědek Department of Pediatrics, Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic