Summary about Disease
Alpha-mannosidosis is a rare, inherited lysosomal storage disorder caused by a deficiency of the enzyme alpha-mannosidase. This enzyme is needed to break down complex sugars called oligosaccharides. When alpha-mannosidase is deficient, these sugars accumulate in various cells and tissues throughout the body, leading to a range of symptoms affecting multiple organ systems. The severity of the disease can vary greatly.
Symptoms
Symptoms can range from mild to severe. Common symptoms include:
Skeletal abnormalities: Dysostosis multiplex (abnormal bone development), joint stiffness, scoliosis, hip dysplasia
Facial features: Coarse facial features, prominent forehead, large tongue
Hearing loss: Often progressive and may lead to deafness
Cognitive impairment: Intellectual disability, developmental delays
Muscle weakness: Hypotonia
Recurrent infections: Particularly respiratory infections
Enlarged liver and spleen: Hepatomegaly and splenomegaly
Hernias: Umbilical and inguinal hernias are common.
Ataxia: Problems with balance and coordination.
Angiokeratoma: Small, dark red spots on the skin.
Causes
Alpha-mannosidosis is caused by mutations in the MAN2B1 gene. This gene provides instructions for making the alpha-mannosidase enzyme. Mutations in this gene lead to a deficiency or complete absence of the enzyme. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Enzyme Replacement Therapy (ERT): Velmanase alfa (Lamzede) is an ERT that provides a functional version of the alpha-mannosidase enzyme. ERT can improve some symptoms and slow disease progression.
Symptomatic treatment: Management of symptoms such as infections, hearing loss, and skeletal problems. This may involve antibiotics for infections, hearing aids, physical therapy, and orthopedic interventions.
Hematopoietic Stem Cell Transplantation (HSCT): In some cases, HSCT may be considered, particularly in individuals with severe disease. HSCT can potentially replace the defective enzyme with a functioning enzyme from the donor cells.
Is Communicable
No, alpha-mannosidosis is not communicable. It is a genetic disorder, meaning it is caused by a gene mutation and cannot be spread from person to person.
Precautions
There are no specific precautions to prevent getting the disease, since it is inherited. Genetic counseling is important for families with a history of alpha-mannosidosis to understand the risk of having an affected child. For individuals with the condition, precautions focus on managing symptoms and preventing complications:
Regular medical monitoring: To track disease progression and manage symptoms.
Preventive measures against infections: Such as vaccinations and good hygiene.
Protective measures for hearing: Regular hearing tests and use of hearing aids as needed.
Physical therapy: To maintain mobility and strength.
How long does an outbreak last?
Alpha-mannosidosis is not an infectious disease that causes outbreaks. It is a chronic, progressive condition that lasts a lifetime. There are periods where symtpoms may be more or less pronounced, but it is a continuous condition.
How is it diagnosed?
Diagnosis typically involves:
Clinical evaluation: Based on the presence of characteristic symptoms.
Enzyme assay: Measuring the level of alpha-mannosidase activity in blood leukocytes or fibroblasts. Low or absent enzyme activity indicates alpha-mannosidosis.
Genetic testing: Confirming the diagnosis by identifying mutations in the MAN2B1 gene.
Urine oligosaccharide analysis: Detects increased levels of mannose-rich oligosaccharides.
Radiological studies: X-rays to assess skeletal abnormalities.
Timeline of Symptoms
The onset and progression of symptoms vary.
Infancy/Early Childhood: Some infants may exhibit subtle symptoms like recurrent infections or mild developmental delays.
Childhood: Symptoms become more apparent, including skeletal abnormalities, hearing loss, coarse facial features, and cognitive impairment.
Adolescence/Adulthood: Symptoms progress, with increasing skeletal problems, ataxia, muscle weakness, and intellectual disability. The rate of progression can vary.
Important Considerations
Early diagnosis: Early diagnosis is crucial to enable early intervention and potentially improve outcomes.
Multidisciplinary care: Management requires a multidisciplinary team of specialists, including geneticists, neurologists, audiologists, orthopedic surgeons, and physical therapists.
Genetic counseling: Genetic counseling is essential for families to understand the inheritance pattern and recurrence risk.
Quality of life: Focus on improving quality of life through symptom management, supportive care, and educational interventions.
Research: Ongoing research is focused on developing new therapies and improving the understanding of the disease.