Mucolipidosis III Gamma

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Mucolipidosis III gamma (ML IIIγ) is a slowly progressive inborn error of metabolism mainly affecting skeletal, joint, and connective tissues. Clinical onset is in early childhood; the progressive course results in severe functional impairment and significant morbidity from chronic pain. Cardiorespiratory complications (restrictive lung disease from thoracic involvement, and thickening and insufficiency of the mitral and aortic valves) are rarely clinically significant. A few (probably <10%) affected individuals display mild cognitive impairment.

Diagnosis/testing: The diagnosis of ML IIIγ is established in a proband with suggestive clinical and radiographic findings and biallelic pathogenic variants in GNPTG identified on molecular genetic testing.

Management: Treatment of manifestations: No measures are known to be effective in treating the progressive limitation of motion in large and small joints. Low-impact physical therapy is usually well tolerated. In older adolescents and adults joint replacement has been successful in relieving hip pain and knee pain. Carpal tunnel signs, and rarely tarsal tunnel symptoms, may require surgical tendon release procedures for temporary relief. Later in the disease course when bone pain of variable intensity may become frequent, management focuses on pain relief. Bisphosphonate treatment in individuals with significant skeletal disease and markedly decreased bone mineral densitometry can be considered. When significant cardiac valvular dysfunction disrupts ventricular function, valve replacement needs to be considered. Addressing the social and emotional needs of affected individuals and their families is recommended.

Surveillance: Yearly outpatient clinic visits (unless more frequent pain, cardiac, and/or respiratory monitoring is warranted) to assess pain level, musculoskeletal needs, gross motor and fine motor function, vision, cardiac and respiratory function, development, educational needs, psychological issues, and utilization of community resources. Frequency of DXA scans depends on age and results of prior studies.

Agents/circumstances to avoid: Vigorous stretching exercises because they are ineffective, painful, and may damage the surrounding joint capsule and adjacent tendons.

Genetic counseling: ML IIIγ is inherited in an autosomal recessive manner. If both parents are known to be carriers of one GNPTG pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the GNPTG pathogenic variants in an affected family member are known, carrier testing for at-risk relatives, prenatal diagnosis for a pregnancy at increased risk, and preimplantation genetic testing are possible.

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