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Diagnostic pathway

A diagnosis of alpha-mannosidosis is suspected based upon a multisymptomatic presentation, a thorough clinical evaluation, a detailed patient history, and results from the diagnostic tests described below4:

Oligosaccharides in urine

A preliminary investigation may be run by measuring mannose-rich oligosaccharide concentrations in urine or serum. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic.4,9

Acid alpha-mannosidosis activity

Diagnosis is confirmed by measuring residual α-mannosidase activity in leukocytes of other nucleated cells via a fluorometric assay.4 This is the most reliable diagnostic method, along with genetic testing.

Peripheral blood examination

Light microscopy or transmission electron microscopy can be used to show vacuoles in bone marrow smears and lymphocytes from peripheral blood in most people with alpha-mannosidosis. However, additional tests are necessary when the disease is suspected.4

Genetic testing

Disease-causing variants may be identified by a number of methods but commonly Next-Generation sequencing is used to sequence the exons of the MAN2B1 gene, followed by DNA sequencing. DNA from peripheral blood cells is used for this type of testing.4

Detect Lysosomal Storage Diseases (LSDs) Genetic Testing Program

Chiesi Global Rare Diseases is a sponsor of the Invitae Detect LSDs program, increasing access to this genetic testing and counseling program—at no additional charge. Together we are bringing patients closer to an accurate diagnosis and appropriate clinical management.

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While third parties and commercial organizations may provide financial support for this program, tests and services are performed by Invitae. Healthcare professionals must confirm that patients meet certain criteria to use the program. Third parties and commercial organizations may receive deidentified patient data from this program, but at no time would they receive patient identifiable information. Third parties and commercial organizations may receive contact information for healthcare professionals who use this program. Genetic testing and counseling are available in the US and Canada. Healthcare professionals and patients who participate in this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any other products or services from Invitae or from third parties or commercial organizations.

Diagnostic algorithm

A diagnostic algorithm for alpha-mannosidosis has been recently proposed by an international group of experts. Two algorithms were proposed, one for patients ≤10 years of age and one for those >10 years of age, both of which can be applied in a variety of settings and may aid in early diagnosis.9

Patients ≤10 years

In younger patients, hearing impairment and/or speech delay are the cardinal symptoms that should prompt the clinician to look for additional symptoms that may provide further diagnostic clues.9

Adapted from Guffon et al. 2019.9

Patients >10 years

Older patients have different clinical presentations, so the presence of cognitive and motor impairment progression and/or psychiatric manifestations should prompt the clinician to assess for other symptoms.9

aIncludes acute psychotic events.

Adapted from Guffon et al. 2019.9