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Alpha Mannosidosis

Overview

Alpha Mannosidosis is a rare disease that is passed down through families. It is a progressive disease, which means that it worsens throughout the span of life. Children and adults with this disease suffer from unusual bone and skeleton growth, uncommon facial features, hearing loss, intellectual disabilities, problems with the immune system, psychiatric disorders (such as anxiety, depression and hallucinations), and behavioral problems. Some people will have mild to moderate symptoms that start to develop in childhood or adolescence, while others may have more severe symptoms that develop from a very early age. The symptoms of Alpha Mannosidosis are extremely varied and affected individuals may not experience all of the possible symptoms.7

 

Alpha Mannosidosis is passed down through families7

While the parents may not have the disease, they could be “carriers” of a faulty gene that causes the disease. If both parents are carriers of the faulty gene, then there is a 25% chance with every pregnancy that the baby will have the disease.7

The faulty gene prevents the normal breakdown of a special type of sugar molecule. Because the sugar is not broken down as it should be, it builds up in many cells of the body, which causes the symptoms of the disease. The gradual build-up of the sugar in the cells is why the disease itself is gradual.4,7

There are many symptoms of Alpha Mannosidosis7

Unusual facial appearance

The face of a child with the disease may only be subtly different, although the head may be larger and rounder with a noticeable forehead. The neck may be short. The nose may be broad with a flat bridge. The lips are often thick.7

Ear infections and hearing problems

The majority of individuals with Alpha Mannosidosis have a degree of hearing loss and are prone to frequent ear infections.7

Poorly formed spine

The bones of the spine (vertebrae) normally line up from the neck to the buttocks. Individuals with Alpha Mannosidosis can have poorly formed vertebrae that may not stably interact with each other.7

Unusual bones and joints

The bones may grow in a way that causes joint stiffness, limited joint movement, and nerve damage. These issues progress over time. An individual with the disease may also develop arthritis at a young age.7

Learning difficulties

Almost all individuals with Alpha Mannosidosis have some level of learning difficulty. Individuals at the less severe end of the spectrum may have mild to moderate learning difficulties, while others may be significantly intellectually disabled from a young age.7

Frequent infections

Frequent infections occur.7

Unusual mouth and teeth

Individuals with Alpha Mannosidosis may have an enlarged tongue and widely-spaced teeth.7

Alpha Mannosidosis usually gets worse throughout life7

CHILDHOOD

A child with the condition may have frequent infections, hearing problems, distinctive facial features and developmental delay. Parents might notice that their child may have some muscle weakness. There may be an unusual feature such as a large head, unusual appearance, maybe a bent back. A child may struggle with hearing.7

DIAGNOSIS

Patients show up in front of the doctor with a variety of symptoms, many of which probably can be influenced by factors such as genetics, medical history, and proactive care. Early diagnosis is important.7

ADULTHOOD

An adult may experience bone problems and difficulties with movement, such as joint problems, swelling, unsteady walking and muscle weakness. There may also be behavioral or psychiatric problems, such as confusion, anxiety, depression or hallucinations.7

LONG-TERM OUTLOOK

Ultimately, patients may become dependent on a wheelchair, as they can no longer walk on their own. Independent living will be difficult. The long-term forecast for the condition is poor. Life expectancy is currently not known.7

Treatment for Alpha Mannosidosis is currently limited7

A diagnosis of Alpha Mannosidosis can have a considerable emotional impact on patients and caregivers, so patients should have access to health care and social services, as well as psychological support.8 Treatment for Alpha Mannosidosis is currently limited to managing some of the symptoms. For example, the symptoms affecting the bones, muscles or joints may require surgery.7

References
  1. ClinicalTrials.gov. Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis (SHAMAN). Available at: https://clinicaltrials.gov/ct2/show/NCT04031066. Last accessed: January 21, 2020.
  2. ClinicalTrials.gov. Learn About Clinical Studies. Available at: https://clinicaltrials.gov/ct2/about-studies/learn. Last accessed: January 21, 2020.
  3. National Institutes of Health. NIH Clinical Research Trials and You. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics. Last accessed: January 21, 2020.
  4. Borgwardt L, Stensland HM, Olsen KJ, et al. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015;10:70.
  5. European Medicines Agency. New enzyme replacement therapy to treat rare genetic disorder alpha-mannosidosis in children and adults. Available at: https://www.ema.europa.eu/en/news/new-enzyme-replacement-therapy-treat-rare-genetic-disorder-alpha-mannosidosis-children-adults. Last accessed: January 21, 2020.
  6. Chiesi. Clinical Trial Transparency and Data Sharing. Available at: https://www.chiesi.com/en/research-and-development/clinical-trial-transparency-and-data-sharing/. Last accessed: January 21, 2020.
  7. Malm D, Nilssen Ø. Alpha-mannosidosis. Orphanet J Rare Dis. 2008;3:21.
  8. Bavisetty S, Grody WW, Yazdani S. Emergence of pediatric rare diseases: Review of present policies and opportunities for improvement. Rare Dis. 2013;1:e23579.