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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.4,7

Acid alpha-mannosidosis activity

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

Genetic testing

Disease-causing mutations may be identified through polymerase chain reaction amplification of MAN2B1 exons, followed by DNA sequencing. DNA from peripheral blood cells is typically used for this type of testing.⁴

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

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.7

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.7

Adapted from Guffon et al. 2019.7

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.7

aIncludes acute psychotic events.

Adapted from Guffon et al. 2019.7