CDG type I (CDGI) disorders result from impaired synthesis of the incomplete lipid linked oligosaccharide (LLO) 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 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, however, thus understanding of the phenotypes is limited.
The current diagnostic test for CDG is 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.
Mutations in the SRD5A3 gene (4q12) have been identified in individuals with intellectual disability and ophthalmologic and cerebellar defects, with transferrin N-glycosylation profiles indicative of a type I congenital disorder of glycosylation (CDG). Characteristics of affected individuals included congenital eye malformations with variable degree of visual loss, nystagmus, muscle hypotonia, motor delay, intellectual disability, and facial dysmorphism. Other features present included microcytic anemia, elevated liver enzymes, coagulation abnormalities, and decreased antithrombin III levels. Common presenting features were ocular coloboma or hypoplasia of the optic disk with cerebellar atrophy or vermis malformation. Sporadic features included ichthyosiform erythroderma, dry skin, and congenital heart malformations.
SRD5A3 mutations were identified in 7 of 40 individuals with CDG type Ix (CDG type I negative for known gene mutations). SRD5A3-related CDG is inherited in an autosomal recessive manner. The protein product of the SRD5A3 gene is necessary for the synthesis of the oligosaccharide precursor used for N-glycoslyation.
- Cantagrel et al. (2010). SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell 142: 203.
- Confirmation of a clinical diagnosis of SRD5A3-Related Congenital Disorder of Glycosylation.
- Carrier testing in adults with a family history of SRD5A3-Related Congenital Disorder of Glycosylation.
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) or ACD (yellow 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.
- 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.