Summary about Disease
Deficiency of alpha-L-iduronidase refers to a group of genetic disorders known as mucopolysaccharidoses type I (MPS I). MPS I is a lysosomal storage disorder caused by a deficiency of the enzyme alpha-L-iduronidase. This enzyme is crucial for breaking down complex sugar molecules called glycosaminoglycans (GAGs), previously known as mucopolysaccharides. When alpha-L-iduronidase is deficient or absent, GAGs accumulate within cells, leading to progressive damage to various organs and tissues. MPS I exists on a spectrum of severity, with the most severe form known as Hurler syndrome, and milder forms including Hurler-Scheie syndrome and Scheie syndrome.
Symptoms
Symptoms vary greatly depending on the severity of the alpha-L-iduronidase deficiency and the specific form of MPS I. Common symptoms include:
Skeletal abnormalities: Dysostosis multiplex (characteristic skeletal changes), joint stiffness, claw hand deformities, short stature, spinal deformities (kyphosis, scoliosis).
Organomegaly: Enlarged liver (hepatomegaly) and spleen (splenomegaly).
Cardiac problems: Heart valve abnormalities, cardiomyopathy.
Respiratory issues: Upper airway obstruction, recurrent respiratory infections, sleep apnea.
Neurological involvement: Cognitive impairment (more severe in Hurler syndrome), hydrocephalus, carpal tunnel syndrome.
Corneal clouding: Opacification of the cornea, leading to vision problems.
Facial features: Coarse facial features, prominent forehead, depressed nasal bridge.
Hernias: Inguinal and umbilical hernias.
Hearing loss: Sensorineural hearing loss.
Causes
MPS I is caused by mutations in the IDUA gene, which provides the instructions for making the alpha-L-iduronidase enzyme. These mutations lead to a deficiency or absence of the enzyme, preventing the proper breakdown of GAGs. MPS I is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. Individuals who inherit only one copy of the mutated gene are carriers and usually do not show symptoms.
Medicine Used
Treatment for MPS I aims to manage symptoms and slow disease progression. Treatment options include:
Enzyme Replacement Therapy (ERT): ERT involves intravenous infusions of a manufactured version of the alpha-L-iduronidase enzyme (laronidase). This helps to reduce GAG accumulation in some tissues and organs.
Hematopoietic Stem Cell Transplantation (HSCT): HSCT, also known as bone marrow transplant, can provide a source of healthy cells that produce the enzyme. It is most effective when performed early in life, particularly in individuals with Hurler syndrome.
Symptomatic Treatment: Management of specific symptoms, such as pain relief, respiratory support, cardiac medications, and surgery for hernias or skeletal abnormalities.
Is Communicable
No, MPS I is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.
Precautions
For individuals with MPS I, precautions focus on managing the complications of the disease:
Regular monitoring: Regular check-ups with specialists (geneticist, cardiologist, pulmonologist, ophthalmologist, etc.) to monitor disease progression and adjust treatment.
Respiratory support: Measures to prevent and treat respiratory infections, including vaccinations and potentially airway management.
Cardiac care: Management of heart conditions, including medication and potential surgery.
Physical therapy: Physical therapy to maintain joint mobility and muscle strength.
Hearing and vision care: Regular hearing and vision assessments and appropriate interventions.
Genetic counseling: Genetic counseling for affected individuals and their families to understand the inheritance pattern and recurrence risk.
How long does an outbreak last?
MPS I is not an outbreak. It is a chronic, progressive genetic condition. There is no "outbreak" period. The condition persists throughout the individual's life, with symptoms gradually worsening over time without treatment. ERT and HSCT can slow the progression of the disease.
How is it diagnosed?
Diagnosis of MPS I typically involves:
Clinical evaluation: Assessment of symptoms, physical examination, and family history.
Urine tests: Measurement of GAG levels in the urine, which are often elevated in individuals with MPS I.
Enzyme assay: Measurement of alpha-L-iduronidase enzyme activity in blood leukocytes or skin fibroblasts. A significantly reduced enzyme activity confirms the diagnosis.
Genetic testing: Identification of mutations in the IDUA gene through DNA sequencing.
Imaging studies: X-rays to assess skeletal abnormalities, echocardiograms to evaluate heart function, and MRI scans to assess neurological involvement.
Timeline of Symptoms
The timeline of symptom onset and progression varies depending on the severity of the MPS I.
Hurler syndrome (severe): Symptoms typically appear in infancy (6-24 months). Rapid progression of developmental delay, skeletal abnormalities, organomegaly, and corneal clouding.
Hurler-Scheie syndrome (intermediate): Symptoms appear later in childhood (3-8 years). Slower progression than Hurler syndrome, with milder cognitive impairment and skeletal abnormalities.
Scheie syndrome (mild): Symptoms may not be apparent until late childhood or adulthood. Slowest progression, with relatively normal intelligence and milder skeletal and cardiac involvement.
Important Considerations
Early diagnosis and treatment are crucial: Early intervention with ERT or HSCT can significantly improve outcomes, particularly for individuals with Hurler syndrome.
Multidisciplinary care: Management of MPS I requires a multidisciplinary team of specialists, including geneticists, cardiologists, pulmonologists, orthopedists, ophthalmologists, and physical therapists.
Family support: Providing emotional and practical support to affected individuals and their families is essential.
Research: Ongoing research is focused on developing new and improved therapies for MPS I.
Newborn screening: Newborn screening for MPS I is becoming more widespread, allowing for earlier diagnosis and treatment.