Understanding Mucopolysaccharidosis Type I (MPS I)
Mucopolysaccharidosis type I (MPS I) is a rare inherited lysosomal storage disorder caused by a deficiency or absence of the alpha-L-iduronidase (IDUA) enzyme. This enzyme is crucial for breaking down long sugar molecules called glycosaminoglycans (GAGs). When the enzyme is missing or dysfunctional, GAGs accumulate in the body's cells, leading to progressive damage to multiple organs and tissues. The condition exists on a spectrum of severity, with what was formerly known as Hurler syndrome at the most severe end.
Over time, medical understanding has evolved, and MPS I is now often described as being either severe (the former Hurler syndrome) or attenuated (less severe). The concept of adult-onset Hurler syndrome is, therefore, misleading, as the severe form is invariably fatal in early childhood. However, adults can be affected by the attenuated forms of MPS I, which were historically known as Hurler-Scheie and Scheie syndromes.
The Spectrum of MPS I: Hurler vs. Attenuated Forms
To understand what is the Hurler syndrome in adults?, it is vital to differentiate between the historical subtypes of MPS I. The core issue remains the same across all subtypes—a buildup of GAGs—but the rate and extent of damage vary dramatically based on the residual enzyme activity.
The Severe Phenotype: Hurler Syndrome (MPS I-H)
The severe form, Hurler syndrome, is characterized by a complete or near-complete lack of IDUA enzyme activity.
- Infancy onset: Symptoms typically appear within the first year or two of life and progress rapidly.
- Multi-systemic damage: Affects numerous body systems, leading to severe skeletal abnormalities (dysostosis multiplex), coarse facial features, heart disease, enlarged organs (hepatosplenomegaly), and progressive intellectual disability.
- Shortened lifespan: Without treatment, children rarely survive past the first decade of life.
The Attenuated Phenotypes: Hurler-Scheie (MPS I-H/S) and Scheie (MPS I-S)
Unlike the severe form, attenuated MPS I is caused by some residual enzyme activity, resulting in a slower progression of the disease.
- Later onset: Symptoms may not appear until later in childhood, adolescence, or even adulthood.
- Milder symptoms: While physical symptoms overlap with the severe form (e.g., joint stiffness, carpal tunnel syndrome, corneal clouding), intellectual function may be near-normal, especially in Scheie syndrome.
- Variable life expectancy: Individuals with attenuated MPS I can live into adulthood, although they still face significant health challenges.
Symptoms of Attenuated MPS I in Adults
Adults with attenuated MPS I experience a range of symptoms, most notably affecting their musculoskeletal, cardiac, and neurological systems. The slow, progressive nature of the disease can lead to chronic, worsening health issues that are often initially misdiagnosed.
Musculoskeletal and Joint Problems
- Joint stiffness and contractures: A progressive loss of joint mobility is common, affecting hands (leading to "claw hand" deformity), hips, and shoulders.
- Carpal tunnel syndrome: Compression of nerves in the wrist due to GAG accumulation is a frequent and often early symptom, leading to pain, numbness, and weakness.
- Skeletal abnormalities: While less severe than in Hurler syndrome, adults may experience skeletal issues like spinal curvature (kyphoscoliosis) and hip problems.
Cardiac and Respiratory Complications
- Heart valve disease: Thickening and leaking of heart valves, particularly the mitral and aortic valves, can lead to heart failure over time.
- Airway obstruction: Accumulation of GAGs in the respiratory tract can cause recurrent respiratory infections and sleep apnea, a major cause of mortality.
Other Manifestations
- Corneal clouding: Progressive clouding of the corneas is a classic sign of MPS I and can lead to vision impairment.
- Hearing loss: A combination of conductive and sensorineural hearing loss is common due to GAG buildup in the middle ear and nerve damage.
- Enlarged organs: Hepatosplenomegaly (enlarged liver and spleen) is often present, though it may not cause significant symptoms itself.
- Neurological issues: Mild cognitive impairment may occur in some attenuated forms, and spinal cord compression can result from dural thickening.
Diagnosis of MPS I in Adults
Given the nonspecific nature of some symptoms, diagnosis of attenuated MPS I in adulthood can be challenging and delayed. It often begins with a thorough clinical examination, followed by specific lab tests.
- Urine tests: Screening for elevated levels of GAGs in the urine is a useful first step.
- Enzyme assay: The definitive diagnosis is confirmed by measuring the IDUA enzyme activity in blood cells (leukocytes) or skin cells (fibroblasts).
- Genetic testing: DNA sequencing can identify the specific mutation in the IDUA gene, which can help predict disease severity and confirm the diagnosis.
Treatment and Management for Adults with MPS I
Treatment for MPS I is supportive and multidisciplinary, aimed at managing symptoms and slowing disease progression. There is currently no cure, but therapies have significantly improved the lives and life expectancy of many individuals with attenuated forms.
Therapeutic Approaches
- Enzyme Replacement Therapy (ERT): Involves weekly intravenous infusions of a recombinant IDUA enzyme (laronidase). While ERT effectively addresses systemic issues like organ enlargement and respiratory problems, it cannot cross the blood-brain barrier and therefore does not impact neurological symptoms.
- Hematopoietic Stem Cell Transplantation (HSCT): A bone marrow or cord blood transplant can provide a new source of functional IDUA enzyme. While typically performed in young children with severe Hurler syndrome, it may be an option for certain patients to improve cognitive outcomes and overall survival.
Symptomatic and Supportive Care
- Cardiovascular care: Regular cardiac monitoring is crucial due to the risk of valve disease.
- Orthopedic surgery: Procedures like carpal tunnel release, joint contracture release, and spinal decompression may be necessary to address musculoskeletal issues.
- Respiratory support: Management of sleep apnea with devices like CPAP or surgery is essential for improving respiratory function.
- Audiology and ophthalmology: Regular checkups are needed to manage hearing loss and corneal clouding.
- Physical and occupational therapy: These therapies are vital for maintaining mobility, joint function, and overall quality of life.
Comparison of MPS I Phenotypes
| Feature | Severe MPS I (Formerly Hurler Syndrome) | Attenuated MPS I (Formerly Hurler-Scheie & Scheie) |
|---|---|---|
| Enzyme Activity | None to very low | Low to moderate residual activity |
| Onset of Symptoms | Early infancy (<2 years) | Later childhood, adolescence, or adulthood |
| Cognitive Function | Severe and progressive decline | Normal to mild impairment |
| Lifespan | Rarely beyond childhood (typically <10 years) | Extended, often into adulthood |
| Skeletal Symptoms | Severe dysostosis multiplex, kyphosis | Milder, progressive joint stiffness, carpal tunnel |
| Corneal Clouding | Early and prominent | Later onset, progressive |
| Treatment Focus | HSCT, ERT, and symptom management | ERT and symptom management |
Conclusion
While the severe form of mucopolysaccharidosis type I (MPS I), known as Hurler syndrome, is a disease of early childhood, the less severe (attenuated) forms can and do affect adults. These adults may live with a progressive, multi-systemic disorder characterized by significant cardiac, skeletal, and sensory problems. With early diagnosis and a comprehensive, multidisciplinary management strategy involving therapies like ERT and supportive care, individuals with attenuated MPS I can experience improved quality of life and prolonged lifespan. The complexity and rarity of the condition necessitate specialized medical care to address the diverse range of symptoms that can emerge throughout an adult's life.
