CDG type I (CDGI) disorders result from impaired synthesis of the lipid linked oligosaccharide (LLO) precursor and/or its attachment to the growing polypeptide chain. CDG-Ia is the most common form reported, due to phosphomannomutase deficiency, an enzyme that converts mannose-6-phosphate to mannose-1-phosphate. CDG-Ib (phosphomannose isomerase, MPI deficiency) is the only known treatable form, by giving mannose orally. CDG type II (CDGII) includes defects in the processing of N-glycans.
Phenotypes of this disorder are extremely variable. Manifestations range from severe developmental delay and hypotonia with multiple organ system involvement beginning in infancy, to hypoglycemia and protein-losing enteropathy with normal development. Most subtypes have been described in only a few individuals, thus understanding of the phenotypes is limited.
The current diagnostic test for CDG is the analysis of serum transferrin glycoforms, also called "transferrin isoforms analysis," or "carbohydrate-deficient transferrin analysis." If positive, this testing can be followed by DNA testing to identify mutations in the gene involved.
Paesold-Burda et al. (2009) identified a homozygous mutation in the COG5 gene (7q22.3) in an individual with CDGIIi. Her features include developmental delay, moderate intellectual disability, a slow and inarticulate speech, mild hypotonia, trunchal ataxia, and pronounced diffuse atrophy of the cerebellum and brain stem.
- Confirmation of a clinical diagnosis of Congenital Disorder of Glycosylation Type IIi.
- Carrier testing in adults with a family history of Congenital Disorder of Glycosylation Type IIi.
Analytical Sensitivity: ~99%
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Analysis of other CDG genes is also available, including single gene analysis and a next generation sequencing panel.
- Biochemical carbohydrate deficient transferrin analysis for CDGs is also available.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.