Alpha-mannosidosis is an autosomal recessive disorder due to deficiency in the lysosomal enzyme alpha-mannosidase. The enzyme is responsible for catalyzing the removal of the mannose sugar residues during the breakdown of proteins that contain sugar groups (called glycoproteins), such as oligosaccharides. Deficiency of the alpha-mannosidase activity results in accumulation of mannose-rich oligosaccharides chains, leading to swelling of the lysosome and impairment of normal cellular functions.
Alpha-mannosidosis is a heterogeneous condition that is classified into overlapping types. Clinical symptoms of Type I, the mildest form, are typically noticeable after 10 years of age and do not include skeletal abnormalities. Clinical symptoms of Type 2, the intermediate form, include skeletal abnormalities and typically onset before 10 years of age. Type 3 is the most severe form with early childhood onset of symptoms and rapid progression of the disease, leading to death. Individuals with alpha-mannosidosis have: delayed motor development, mental retardation, hearing loss, typical facies (a Hurler-like face), bone disease, immunodeficiency, ocular findings and hepatosplenomegaly. In addition, psychiatric problems are common.
Mutations in the MAN2B1 gene are responsible for alpha-mannosidosis(1). More than 20 different disease causing mutations have been identified. These mutations include missense, nonsense, splice site, frameshift and large deletions(2). These mutations lead to partial or complete loss of enzymatic activity.
For questions about testing for alpha-mannosidosis, call the Emory Genetics Laboratory at (404) 778-8500(404) 778-8500 or (800) 366-1502(800) 366-1502.
For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565(404) 778-8565 or (800) 200-1524(800) 200-1524.
For patients with mutations not identified by full gene sequencing, a separate deletion/duplication assay is available using a targeted CGH array KU.
1). Nilssen O et al. alpha-Mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings. 1997. Hum Mol Genet. 6:717-726.
2). Berg et al. Spectrum of mutations in alpha-mannosidosis. 1999. Am J Hum Genet. 64:77-88
- Confirmation of a clinical diagnosis of alpha-mannosidosis
- Prenatal testing for known familial mutation(s).
- Assessment of carrier status in high risk family members - known mutation analysis.
Detection and Reference Range
Clinical Sensitivity: In 43 individuals, mainly of European origin, with alpha mannosidosis, Bert et al. identified 62 mutations, giving a detection rate of 72% .
Analytical Sensitivity: ~99%
Prevalence: The estimated prevalence of all lysosomal storage disorders is 2-5 per 100,000. The prevalence of alpha-mannosidosis disease is not specifically known, but is likely to be rare and may vary by ethnicity.
Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition. Contact the laboratory if further information is needed.
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.
- Known mutation analysis (Custom Diagnostics) is available to test family members.
- A deletion/duplication assay is available separately for individuals where mutations are not identified by sequence analysis. Refer to the test requisition or contact the laboratory for more information.
- Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor for specific requirements for prenatal testing before collecting a fetal sample.