Skip to content
Healthy Aging Hub

What is the life expectancy of someone with mucolipidosis type 3?

4 min read
Genetic Disorders Pediatrics Lysosomal Storage Disorders

According to a 2021 systematic review of 843 mucolipidosis cases, the median survival for individuals with mucolipidosis type 3 (MLIII) was 62 years, with a median age of death reported as 33 years. However, it is important to note that the life expectancy of someone with mucolipidosis type 3 varies widely, depending heavily on the specific subtype and the severity of symptoms. This condition is milder than mucolipidosis type 2 (MLII), with a slower disease progression and survival well into adulthood for many individuals.

Quick Summary

Mucolipidosis type 3 (MLIII) is a progressive lysosomal storage disorder with a wide range of prognoses, depending on the subtype and symptom severity. Many individuals with MLIII survive into adulthood, but potential cardiac and respiratory complications may shorten their lifespan. Management focuses on supportive care to address progressive skeletal, joint, and connective tissue problems.

Key Points

  • Median Survival is ~62 years: A 2021 review found a median survival of 62 years for individuals with mucolipidosis type 3, though it varies by subtype.

  • Wide Prognostic Range: Life expectancy is highly variable, with some individuals living into late adulthood and others experiencing more severe, life-limiting complications earlier.

  • Cardiac and Respiratory Issues: The most common causes of a shortened lifespan are cardiac complications, such as heart valve disease, and respiratory insufficiency due to skeletal abnormalities.

  • Subtypes Influence Severity: The MLIII alpha/beta subtype, caused by GNPTAB mutations, can be more severe than the milder MLIII gamma subtype, caused by GNPTG mutations.

  • Supportive Care is Key: While there is no cure, managing symptoms through physical therapy, pain medication, and monitoring cardiac health can significantly improve an individual's quality of life.

In This Article

What influences the life expectancy for MLIII?

Several key factors influence the prognosis and life expectancy of an individual with mucolipidosis type 3 (MLIII):

  • Disease subtype: MLIII has two subtypes, MLIII alpha/beta and MLIII gamma, which correlate with different genetic mutations and disease courses. MLIII alpha/beta can have a wide phenotypic range, while MLIII gamma is generally milder.
  • Symptom severity: The rate at which skeletal, joint, and cardiac issues progress varies significantly among patients. Those with less severe symptoms and later-onset complications generally have a longer lifespan.
  • Cardiac complications: Heart valve abnormalities and cardiovascular disease are common in MLIII and are one of the most frequent causes of premature death in mucolipidosis patients.
  • Respiratory complications: Restrictive lung disease caused by skeletal abnormalities in the spine and ribs can reduce lung capacity, particularly in adults, and lead to cardiorespiratory insufficiency.
  • Medical management: Proper medical care, including pain management, orthopedic surgeries, and monitoring of cardiac health, can improve quality of life and potentially extend life expectancy.

Genetic basis and subtypes of mucolipidosis type 3

Mucolipidosis type 3 is a rare autosomal recessive lysosomal storage disorder caused by mutations in either the GNPTAB or GNPTG gene. These genes are responsible for producing the enzyme N-acetylglucosamine-1-phosphotransferase, which is crucial for tagging lysosomal enzymes for transport.

There are two main subtypes based on the affected gene:

  • MLIII alpha/beta: Caused by mutations in the GNPTAB gene, this subtype can range from intermediate to attenuated severity. While still milder than MLII, some severely affected MLIII alpha/beta patients may not survive into adulthood.
  • MLIII gamma: Caused by mutations in the GNPTG gene, this is typically the mildest form of mucolipidosis. Most individuals with MLIII gamma survive into adulthood, although they may experience progressive joint pain and stiffness.

Comparison of mucolipidosis types II and III

Mucolipidosis type 3 is an attenuated, or milder, form of mucolipidosis type 2 (MLII), and understanding the differences highlights why the life expectancy varies dramatically between the two.

Feature Mucolipidosis Type II (MLII) Mucolipidosis Type III (MLIII)
Onset of symptoms At birth or early infancy. Typically around 3 years of age, and sometimes later in childhood.
Enzyme activity Complete or near-complete absence of GlcNAc-1-phosphotransferase activity. Partial deficiency of GlcNAc-1-phosphotransferase activity, allowing for some function.
Intellectual function Severe psychomotor and intellectual disability. Mostly normal intellectual capacity, with mild learning problems possible in some.
Progression Rapidly progressive and severe. Slowly progressive over many years.
Life expectancy Generally do not survive beyond early childhood. Many survive into adulthood, often into their 40s, 50s, or beyond, depending on the subtype and severity.

Management and impact on quality of life

While there is currently no cure or disease-modifying treatment for MLIII, management focuses on supportive care to address the symptoms and improve quality of life.

  • Musculoskeletal care: This is a primary concern due to progressive joint stiffness, pain, and skeletal abnormalities. Patients often require physical therapy, pain medication, and sometimes orthopedic surgeries like joint or hip replacements.
  • Cardiovascular monitoring: Regular monitoring of heart valve function is critical to detect and manage potential cardiac issues, which can be life-threatening.
  • Pain management: Chronic bone and joint pain significantly impacts quality of life and requires careful management, sometimes including the use of bisphosphonates to increase bone density.
  • Regular surveillance: Multidisciplinary care with regular check-ups is essential to monitor symptoms, especially pain levels, respiratory function, and mobility.

Conclusion

The life expectancy of an individual with mucolipidosis type 3 is significantly longer and has a much wider range than for those with the more severe MLII, with many people surviving into adulthood. However, the prognosis is highly dependent on the specific subtype and the rate of symptom progression, especially related to cardiac and respiratory function. While progressive joint pain, stiffness, and skeletal abnormalities impact quality of life, comprehensive medical and supportive care can help manage these challenges. With proper management and surveillance, many individuals with MLIII can lead meaningful lives for several decades, though complications like cardiorespiratory insufficiency are often the ultimate cause of a shortened lifespan. Given the rarity of the disease, ongoing research is crucial to better understand its natural history and develop effective therapies.

Disclaimer: The information in this article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.

Sources

Frequently Asked Questions

Mucolipidosis type 3 (MLIII) is an attenuated, or milder, form of mucolipidosis type 2 (MLII). MLII is caused by a complete lack of the enzyme GlcNAc-1-phosphotransferase, leading to severe symptoms and a very short life expectancy. MLIII is caused by a partial deficiency of this enzyme, resulting in a slower, less severe disease progression and a longer life expectancy.

Most individuals with mucolipidosis type 3 have normal intellectual capacity, distinguishing it from the severe cognitive impairment seen in MLII. However, some patients, particularly with the MLIII alpha/beta subtype, may experience mild intellectual disability or learning problems.

Common symptoms include progressive joint stiffness (especially in the shoulders, hips, and fingers), short stature, skeletal abnormalities (dysostosis multiplex), low bone mineral density (osteoporosis), and mild coarsening of facial features. Cardiac valve abnormalities and pain are also common.

No, there is currently no cure or disease-modifying treatment available for mucolipidosis type 3. Treatment is focused on managing symptoms and providing supportive care, such as pain management, physical therapy, and surgical interventions for joint or cardiac issues.

Diagnosis involves clinical and radiological examination, as well as laboratory testing. This includes measuring lysosomal enzyme activity in plasma and fibroblasts, which will show elevated levels in plasma and decreased levels within cells. Molecular genetic testing to identify mutations in the GNPTAB or GNPTG genes confirms the diagnosis.

Yes, heart valve abnormalities and other cardiac issues are monitored closely. If significant heart valve dysfunction occurs, surgical options such as valve replacement may be necessary. These procedures are sometimes considered life-extending.

Mucolipidosis type 3 is inherited in an autosomal recessive pattern. This means that for a child to be affected, they must inherit two mutated gene copies, one from each parent. The parents, who are typically unaffected carriers, each have a 25% chance of passing the condition on to their child with each pregnancy.

References

  1. 1
    Mucolipidosis type II and type III: a systematic review of 843 cases
  2. 2
    Mucolipidosis alpha/beta
  3. 3
    Mucolipidosis type III
  4. 4
    Mucolipidosis III Gamma
  5. 5
    Mucolipidosis III (ML III)
  6. 6
    Case Report: Mucolipidosis II and III Alpha/Beta Caused by Compound Heterozygous GNPTAB Mutations in Two Unrelated Families

Related Topics

#Rare Genetic Disease #lysosomal storage disorder #mucolipidosis type 3 #MLIII life expectancy #pseudo-hurler polydystrophy #GNPTAB gene #GNPTG gene #inherited metabolic disorders

Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice. Always consult a qualified healthcare provider regarding personal health decisions.