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Alpha-mannosidosis
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Alpha-mannosidosis

Alpha-mannosidosis is a rare inherited lysosomal storage disorder that causes progressive damage to multiple organs and tissues. It is characterized by intellectual disability, distinctive facial features, skeletal abnormalities, and neurological deterioration.

Overview

Alpha-mannosidosis is a rare inherited disorder that affects many organs and tissues of the body. The signs and symptoms of this condition can range from mild to severe. In its most severe, early-onset form, the disorder appears in infancy with rapid progression and severe neurological decline, and affected individuals often do not survive past childhood. In the most extreme cases, an affected fetus may die before birth. Conversely, individuals with later-onset alpha-mannosidosis experience milder symptoms that progress more slowly, with some surviving into their fifties. The mildest cases may only be detected through laboratory testing and result in few, if any, symptoms.

Symptoms

People with alpha-mannosidosis can experience a wide range of physical, neurological, and psychiatric symptoms:

Physical and Skeletal Features

  • Distinctive facial features, which can include rounded eyebrows, large ears, a flattened bridge of the nose, and overgrown gums.
  • Reduced bone density (osteopenia).
  • Thickening of the bones at the top of the skull (calvaria).
  • Deformations of the bones in the spine.
  • Deterioration of the bones and joints.
  • Enlargement of the liver and spleen (hepatosplenomegaly).

Neurological and Sensory Symptoms

  • Intellectual disability.
  • Difficulty coordinating movements (ataxia).
  • Muscle weakness (myopathy).
  • Delay in developing motor skills, such as sitting and walking.
  • Speech impairments.
  • A buildup of fluid in the brain (hydrocephalus).
  • Hearing loss.
  • Clouding of the lens of the eye.

Other Symptoms

  • Increased risk of infections.
  • Psychiatric symptoms, including depression, anxiety, or hallucinations. These episodes of psychiatric disturbance may be triggered by stressors such as surgery, emotional upset, or changes in routine.

Causes

Mutations in the MAN2B1 gene cause alpha-mannosidosis. This gene provides instructions for producing the enzyme alpha-mannosidase. This enzyme operates within lysosomes, which are specialized compartments that digest and recycle materials inside the cell.

Normally, alpha-mannosidase helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins), specifically those containing a sugar molecule called mannose. Mutations in the MAN2B1 gene interfere with the enzyme's ability to perform this role. As a result, mannose-containing oligosaccharides abnormally accumulate in the lysosomes, causing cells to malfunction and eventually die. This cellular damage and death lead to the characteristic features and organ damage of alpha-mannosidosis.

Associated Genes

  • MAN2B1

Inheritance

This condition is inherited in an autosomal recessive pattern. This means that both copies of the gene in each cell must have mutations for the individual to be affected. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • Alpha-D-mannosidosis
  • Alpha-mannosidase B deficiency
  • Alpha-mannosidase deficiency
  • Deficiency of alpha-mannosidase
  • Lysosomal alpha B mannosidosis
  • Lysosomal alpha-D-mannosidase deficiency
  • Mannosidosis

Additional Resources

  • Genetic Testing Registry: Deficiency of alpha-mannosidase
  • Genetic and Rare Diseases Information Center: Alpha-mannosidosis
  • National Organization for Rare Disorders (NORD)
  • ClinicalTrials.gov
  • OMIM: MANNOSIDOSIS, ALPHA B, LYSOSOMAL; MANSA
  • PubMed

Frequently Asked Questions

Diagnosis typically involves a blood test to measure the activity of the alpha-mannosidase enzyme in white blood cells, which will be significantly reduced in affected individuals. This is often followed by genetic testing to identify mutations in the MAN2B1 gene, which confirms the diagnosis and can help predict the severity and progression of the disorder.
Enzyme replacement therapy (ERT) with velmanase alfa is an approved treatment that provides the missing alpha-mannosidase enzyme, helping to reduce the accumulation of harmful substances in cells. This can slow disease progression and improve some symptoms, particularly skeletal and neurological manifestations. Bone marrow transplantation (hematopoietic stem cell transplantation) is another option, especially for severe forms, which can provide a source of healthy enzyme-producing cells.
Ongoing monitoring is crucial and includes regular neurological assessments, hearing tests, eye exams for cataracts, skeletal evaluations (X-rays, bone density scans), and cardiac assessments. Supportive care involves physical therapy for motor skills and joint mobility, speech therapy, educational support for intellectual disability, and management of recurrent infections, which may require immunoglobin replacement therapy.
The early-onset form (Type II/III) typically presents in infancy with rapid neurological decline, severe intellectual disability, and a significantly reduced life expectancy, often not surviving past childhood. The later-onset form (Type I) has milder symptoms that progress more slowly, with individuals potentially surviving into their fifties or beyond, experiencing less severe intellectual disability and a slower progression of physical and neurological symptoms. Some mild cases may even be asymptomatic or only detected incidentally.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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