Mannosidosis. New clinical presentation, enzyme studied, and carbohydrate analysis

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Mannosidosis is a rare lysosomal storage disease caused by alpha-mannosidase deficiency.
• This deficiency leads to the accumulation of mannose-rich complex carbohydrates in tissues.
• It is an inherited metabolic disorder affecting multiple organ systems.

Observation:

• Two unrelated males, aged 6 and 26, with nonprogressive encephalopathy and moderate intellectual disability were studied.
• The older patient presented with unique massive gingival hyperplasia, a feature not commonly associated with mannosidosis.
• Histiocytes in the hyperplastic gums contained glycoprotein material, suggesting widespread storage.

Findings:

• The ratio of mannose to other urinary carbohydrates effectively determined mannose storage.
• Alpha-mannosidase deficiency was most reliably detected at pH values below 4.0.
• Zinc demonstrated in vitro activation of the mutant enzyme, indicating potential therapeutic avenues.

Implications:

• Early identification of mannosidosis is crucial for management and intervention.
• Screening individuals with intellectual disability and Hurler-like features, particularly with gum hyperplasia, is advised.
• The findings suggest a potential therapeutic strategy involving zinc supplementation for mannosidosis.