Understanding Alpha-Mannosidosis: Causes, Symptoms, Diagnosis, and Treatment

2023-06-14 10:36:14

Alpha-mannosidosis is a lysosomal storage disease that is based on a genetic defect and is a rare disease with an estimated prevalence of 1-2 in 1,000,000 people.¹ Despite its rarity, it is worth knowing about the disease because there are various treatment options that can help patients.

How is Alpha Mannosidosis Caused?

The affected gene is responsible for the expression of the enzyme alpha-mannosidase, which is required for the breakdown of mannose-rich oligosaccharides in the lysosomes of the cells. Due to the loss of function of the enzyme, the complex sugar molecules accumulate in the lysosomes over time and cause cell damage. The pathological effects of alpha-mannosidosis can be very variable, but in each case there is a progressive course that can have a major impact on the quality of life of those affected over time.^2,3

What are the symptoms?

Possible symptoms of alpha-mannosidosis include facial dysmorphism, hearing loss, recurring infections and, as the disease progresses, also cognitive impairment. In addition, movement restrictions usually occur due to skeletal effects or myopathy in those affected.^2,4 You can see other typical key symptoms of the disease in the following figure:

The clinical presentation of alpha-mannosidosis can vary greatly depending on the severity of the disease. In addition, as the disease progresses, the pathologic implications may change over time, often resulting in a long delay in disease recognition.^2,4

How is the diagnosis made?

Since the symptoms mentioned can be very similar to those of other lysosomal storage diseases such as mucopolysaccharidoses (MPS), a differential diagnosis for alpha-mannosidosis should also be carried out if MPS is suspected, and vice versa. Various tests are available for this. So allow z. B. dry blood tests via dry blood card a quick and easy differential diagnosis. You can find more information on the diagnostic procedures and differential diagnostics here. In addition to identifying the typical symptoms, the complete diagnosis of alpha-mannosidosis includes an intensive medical history and various diagnostic tests such as enzymatic analyzes or molecular genetic examinations.²

Since the first symptoms of lysosomal storage diseases often appear in early childhood, it makes sense to use the U7a examination if there are any abnormalities in order to be able to rule out a possible disease. In our U7a brochure we have, in close cooperation with the MPS Society, summarized the typical characteristics of various MPS diseases and also those of alpha-mannosidosis. The brochure also contains a questionnaire for systemic inquiry into a lysosomal storage disease.

How can it be treated?

A number of causal and symptomatic therapeutic approaches are available to treat alpha-mannosidosis. Causal treatment options include hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). While in HSCT healthy donor cells are transplanted into the recipient tissue, in ERT the defective enzyme is synthetically produced and fed to the patient.^2,4 In addition to causal treatments, symptomatic therapeutic approaches should also be carried out in order to improve the quality of life of those affected and reduce their level of suffering. Depending on the symptoms, various treatments from areas such as orthopaedics, otolaryngology or infectiology should be considered.²

Please visit our Rare Diseases websiteto get more exciting information about alpha-mannosidosis and other rare diseases. Here we address, among other things, the basics of the disease, typical symptoms and details of diagnosis and therapy. It also offers an area for those affected and their relatives, in which important information on alpha mannosidosis is presented in a clear and easy-to-understand manner.

Photo credit: iStock.com/solidcolours

Credentials:

1. Beck M, et al. Orphanet J Rare Dis. 2013;8:88.
2. Malm D, Nilssen Ø. Orphanet J Rare Dis. 2008;3:21.
3. Borgwardt L et al. Orphanet J Rare Dis. 2015;10:70.
4. Malm D, Nilssen O. Alpha Mannosidosis. NCBI. 2001. https://www.ncbi.nlm.nih.gov/books/NBK1396/ (Last accessed March 2023)
5. Grosse H. Pediatrics. 2018;30:30.