Summary about Disease
Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by the absence or malfunction of specific lysosomal enzymes needed to break down complex sugar molecules called glycosaminoglycans (GAGs), formerly known as mucopolysaccharides. Because the body can't break down these GAGs, they accumulate in cells, blood, and connective tissues. This storage leads to progressive cellular damage and organ dysfunction, resulting in a variety of physical and mental problems. Different types of MPS exist, each resulting from a deficiency in a specific enzyme.
Symptoms
Symptoms vary widely depending on the specific type of MPS and the severity of the enzyme deficiency. Common symptoms include:
Skeletal abnormalities (e.g., dwarfism, joint stiffness, spinal deformities)
Coarse facial features
Clouding of the cornea
Hearing loss
Enlarged organs (liver, spleen)
Heart valve problems
Developmental delay and intellectual disability (varying degrees)
Respiratory problems (e.g., frequent infections, sleep apnea)
Hernias
Carpal tunnel syndrome
Hydrocephalus
Causes
MPS diseases are caused by genetic mutations in genes that code for specific lysosomal enzymes. These mutations are inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent). If both parents are carriers (have one copy of the mutated gene and one normal copy), there is a 25% chance with each pregnancy that the child will inherit both mutated genes and develop MPS, a 50% chance the child will be a carrier, and a 25% chance the child will inherit two normal genes and be unaffected. Hunter syndrome (MPS II) is an exception, as it is inherited in an X-linked recessive pattern, primarily affecting males.
Medicine Used
Treatment for MPS focuses on managing symptoms and slowing disease progression.
Enzyme Replacement Therapy (ERT): Available for some MPS types (e.g., MPS I, MPS II, MPS IVA, MPS VI), ERT involves intravenous infusions of the deficient enzyme. It can help reduce GAG accumulation and improve some symptoms, but it doesn't cross the blood-brain barrier effectively and may not address neurological symptoms.
Hematopoietic Stem Cell Transplantation (HSCT): HSCT (bone marrow transplant or stem cell transplant) can be used, particularly in MPS I, to provide a source of healthy cells that produce the missing enzyme. It can improve some symptoms and potentially slow disease progression, especially if performed early in life. However, it carries significant risks.
Substrate Reduction Therapy (SRT): SRT aims to reduce the production of GAGs. Eliglustat is approved for some patients with MPS I.
Symptomatic Treatment: Medications and therapies are used to manage specific symptoms, such as pain relievers, heart medications, respiratory support, physical therapy, and occupational therapy.
Gene Therapy: is being tested in clinical trials as a potential treatement.
Is Communicable
No, MPS diseases are not communicable. They are genetic disorders and cannot be spread from person to person.
Precautions
Since MPS is a genetic disorder, there are no precautions to prevent its "acquisition" in the traditional sense of preventing an infection. However, the following is relevant:
Genetic Counseling: Families with a history of MPS should seek genetic counseling to understand the risks of having a child with the disorder.
Prenatal Testing: Prenatal testing, such as chorionic villus sampling (CVS) or amniocentesis, can be performed to determine if a fetus is affected by MPS if there is a known risk.
Newborn Screening: Some regions include MPS I in their newborn screening programs, allowing for early diagnosis and treatment.
How long does an outbreak last?
MPS is not an infectious disease, so the concept of an "outbreak" doesn't apply. MPS is a chronic, progressive condition that lasts throughout a person's lifetime. Symptoms typically worsen over time.
How is it diagnosed?
Diagnosis of MPS typically involves a combination of:
Clinical Evaluation: Assessment of symptoms and physical examination.
Urine Tests: Measuring the levels of GAGs in the urine can indicate an MPS disorder.
Enzyme Assays: Measuring the activity of specific lysosomal enzymes in blood, fibroblasts, or other tissues confirms the specific type of MPS.
Genetic Testing: DNA sequencing can identify the specific mutations in the genes that cause MPS.
Imaging Studies: X-rays, MRI, and echocardiograms are used to assess skeletal abnormalities, organ size, and heart function.
Timeline of Symptoms
The timeline of symptom onset and progression varies depending on the type and severity of MPS.
Early Infancy/Childhood: Some MPS types (e.g., severe forms of MPS I) may present with symptoms in infancy, such as hernias, frequent respiratory infections, and developmental delays. Other types may have a more gradual onset.
Childhood/Adolescence: As the child grows, skeletal abnormalities, coarse facial features, organ enlargement, and developmental delays become more apparent.
Adulthood: In some milder forms of MPS, symptoms may not become fully apparent until adulthood. Progression varies, but typically involves worsening of skeletal problems, heart disease, respiratory problems, and neurological decline.
Important Considerations
Multidisciplinary Care: Management of MPS requires a multidisciplinary team of specialists, including geneticists, pediatricians, neurologists, cardiologists, orthopedists, pulmonologists, and therapists.
Early Diagnosis and Treatment: Early diagnosis and initiation of treatment (ERT, HSCT, SRT) can improve outcomes and slow disease progression in some MPS types.
Quality of Life: Focus on improving quality of life through symptom management, supportive care, and access to resources.
Research: Ongoing research is exploring new therapies, including gene therapy, to improve the treatment of MPS.
Family Support: MPS can be emotionally and physically challenging for families. Access to support groups and counseling is important.