Congenital Disorder Of Glycosylation, Type If

A number sign (#) is used with this entry because congenital disorder of glycosylation type If (CDG1F) is caused by homozygous or compound heterozygous mutation in the MPDU1 gene (604041) on chromosome 17p13.

Description

Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin. For a general discussion of CDGs, see CDG Ia (212065) and CDG Ib (602579).

Clinical Features

Schenk et al. (2001) described 3 unrelated patients with clinical features consistent with a congenital disorder of glycosylation. Patient 'S' had intractable seizures from birth, severe feeding difficulties, no psychomotor development, and patchy desquamation over his entire body. His seizures worsened, accompanied by recurrent apnea leading to his death at age 10 months. Patient 'L' had hypertonia, an ichthyosis-like skin disorder, and psychomotor and growth retardation. At age 16 years, she had severe dwarfism, a developmental level of 1 year, and unchanged skin disease. Patient 'A' had severe psychomotor retardation but no growth or skin problems; he had seizures that responded well to valproate. At the age of 10 years his developmental age was about 2.5 years. Isoelectric focusing of serum transferrin from the 3 patients revealed hypoglycosylation in a type I-like pattern. The patients' fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation, and transfer of incomplete oligosaccharides to protein was detected.

Kranz et al. (2001) reported a patient with CDG If who had severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision.

Molecular Genetics

In 3 unrelated patients with type I CDG, Schenk et al. (2001) identified mutations in the MPDU1 gene: 2 patients ('S' and 'A') of consanguineous parents were homozygotes (604041.0001 and 604041.0002, respectively) and the other (patient 'L') was a compound heterozygote (604041.0003 and 604041.0004). Defects in MPDU1 defined a new glycosylation disorder, CDG If.

In a patient with CDG If, Kranz et al. (2001) identified a homozygous point mutation in the MPDU1 gene (604041.0005). The parents were not known to be consanguineous, but both families had lived in the same village for generations. Kranz et al. (2001) stated that this was the first glycosylation disorder to affect the use, rather than the biosynthesis, of donor substrates for lipid-linked oligosaccharides.