J. Inher. Metab. Dis. 19 (1996) 787-791 © SSIEMand KluwerAcademicPublishers.Printedin the Netherlands Congenital nephrotic syndrome: A novel phenotype of type I carbohydrate-deficient glycoprotein syndrome M. S. VAN DER KNAAP 1., R. A. WEVERS 4, L. MONNENS 5, C. JAKOBS 2, J. JAEKEN 6 and J. A. E. VAN WIJK3 Department of Pediatrics, ~Division of Child Neurology, 2Laboratory of Metabolic Diseases, 3Division of Child Nephrology, Free University ttospital, Amsterdam, 4Laboratory of Pediatrics, SDepartment of Pediatrics, Division of Child Nephrology, University Hospital St Radboud, Nijmegen, The Netherlands; 6Department of Pediatrics, University of Leuven, Leuven, Belgium *Correspondence: Department of Pediatrics, Division of Child Neurology, Free University Hospital, PO Box 7057, 1007 MB Amsterdam, The Netherlands MS received 7.5.96 Accepted 25.6.96 Summary: Type I carbohydrate-deficient glycoprotein (CDG) syndrome is a genetic multisystem disorder generally without overt renal problems. We report a neonate with neurological abnormalities and congenital nephrotic syndrome of diffuse mesangial sclerosis type. Serum transferrin isoelectric focusing showed the typical abnormalities of type I CDG syndrome. Normal transferrin focusing findings in other patients with similar renal problems excluded the possibility of a secondary biochemical phenomenon. The diagnosis of type I CDG syndrome was confirmed by demon- stration of a deficiency of phosphomannomutase. No evidence of pontocerebellar atrophy was found in imaging or at autopsy. We conclude that congenital nephrotic syndrome may occur in type I CDG syndrome, and that this diagnosis should be considered in patients with congenital nephrotic syndrome. Absence of pontocerebellar atrophy does not exclude the diagnosis of type I CDG syndrome. Carbohydrate-deficient glycoprotein (CDG) syndrome type I (McKusick 212065) is a genetic multisystem disorder characterized by a defect in glycosylation of glycoproteins (Jaeken 1991). Isoelectric focusing of serum transferrin shows a marked increase in both asialo- and disialotransferrin and a pronounced decrease of tetra- and pentasialotransferrin (Jaeken et al 1993). In the neonatal and infantile period, characteristic findings in CDG syndrome type I include hypotonia, hyporeflexia, failure to thrive, feeding difficulties, diarrhoea, severe developmental delay, abnormal eye movements, presence of inverted nipples, protrusion of the thorax, fat pads over the buttocks and limb joint restrictions (Hagberg et al 1993). On neuroimaging, signs of pontocerebellar atrophy are found (Akaboshi et al 1995; Jensen 787