Congenital disorder of glycosylation type Ia: a non-progressive encephalopathy associated with multisystemic involvement.

Dr. Jaime Moritz Brum – Laboratório de Genética Bioquímica 00SMHS Quadra 501 Bloco A 70335-901 Brasília DF Brasil. E-mail: [email protected] Congenital disorders of glycosylation (CDG) are a group of severe, autosomal recessive, multisystemic diseases, characterized by abnormal glycosylation of glycoproteins and glycolipids. The first disease of this group was reported in 1980. Since then, at least 16 entities were recognized and were classified in two groups (CDG-Ia to IL and CDG-IIa to IId). Each disease is caused by a specific enzymatic deficiency. CDG-Ia is related to deficient phosphomannomutase activity and represents 80% of CDG type I. The enzyme is coded by PMM2, a gene situated in chromosomal segment 16p13. The estimated prevalence of CDG-Ia is as high as 1:20000 newborns among caucasians, therefore making this disease one of the most common metabolic disorders. CDG-Ia has a broad spectrum of age-related clinical findings with variation even within the same sibship. Table 1 lists the most important clinical features. Failure to thrive, gastrointestinal and neurologic symptoms predominate in the neonatal period and infancy. The most important features during childhood are hypotonia, ataxia, mental retardation, joint contractures, and pigmentary retinopathy. It is estimated that 20% of patients die during the first year of life due to severe infection, liver insufficiency or cardiomyopathy. Some patients develop multiorgan system failure. There is no neurologic regression. Muscle atrophy, peripheral neuropathy and secondary skeletal deformities ensue during adolescence. Some patients survive into adulthood. Adults have premature aging and hypergonadotropic hypogonadism occurs in females. When CDG is suspected, a serum sample is analyzed for transferrin hypoglycosylation by isoelectric focusing or other available method. Diseases like galactosemia and hereditary fructose intolerance must be ruled out, as they are known to cause false-positive results on transferrin isoelectric focusing. The diagnosis of CDG-Ia is confirmed by assay of phosphomannomutase, which is deficient in either leukocytes or fibroTable 1. Clinical manifestations of CDG-Ia.