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 EGL Genetics at 470-378-2200 or 855-831-7447.
For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565 or (800) 200-1524.
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
Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient's clinical and/or biochemical phenotype.
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 EGL Genetics, please submit a copy of the sequencing report with the test requisition. Contact the laboratory if further information is needed.
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
- Known mutation analysis (Custom Diagnostics) is available to test family members.
- 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.