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mucolipidosis type IIIa


Friday 17 February 2006


Definition: Mucolipidosis alpha/beta (ML III alpha/beta) (pseudo-Hurler polydystrophy) is a slowly progressive disorder with clinical onset at approximately age three years. The phenotype is closed from Hurler disease.

Mucolipidosis alpha/beta (ML III alpha/beta) (pseudo-Hurler polydystrophy) is characterized by slow growth rate.

Radiographic evidence of mild to moderate dysostosis multiplex; joint stiffness and pain initially in the shoulders, hips, and fingers; gradual mild coarsening of facial features; and normal to mildly impaired cognitive development. If present, organomegaly is mild.

Pain from osteoporosis that is clinically and radiologically apparent in childhood becomes more severe in older individuals.

Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left ventricular hypertrophy) are common causes of death, typically in early to middle adulthood.


In ML III alpha/beta the activity of nearly all lysosomal hydrolases is up to tenfold higher in plasma and other body fluids than in normal controls because of inadequate targeting to lysosomes.

Urinary excretion of oligosaccharides (OSs), a nonspecific finding, can be excessive but is not always present.

Significant deficiency (1%-10% of normal) of the activity of the enzyme UDP-N-acetylglucosamine: lysosomal hydrolase N-acetylglucosamine-1-phosphotransferase (GNPTA), encoded by GNPTAB, confirms the diagnosis.

Bidirectional sequencing of the entire GNPTAB coding region detects two disease-causing mutations in more than 95% of individuals with ML III alpha/beta.

Such testing is clinically available; duplication/deletion analysis is also available. Management.


Low-impact physical therapy is usually well tolerated. Myringotomy tube placement should be used with caution in the treatment of recurrent otitis media.

Carpal tunnel signs may require tendon release. In late childhood or early adolescence relief of hip pain following exercise becomes important; in older adolescents and adults with milder phenotypic variants, bilateral hip replacement has been successful.

Later in the disease course management focuses on relief of general bone pain associated with osteoporosis, which has responded in a few individuals to monthly IV administration of the bisphosphonate pamidronate.

Prevention of secondary complications: Because of concerns about airway management, surgical intervention should be undertaken only in tertiary care settings with pediatric anesthesiologists and intensivists.


Twice-yearly outpatient clinic visits for young children; annual routine follow-up visits after age six years unless bone pain, deteriorating ambulation, and/or cardiac and respiratory monitoring need more frequent attention.

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

Genetic counseling

ML III alpha/beta is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has 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.

Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

See also

- Hurler disease


- Mucolipidosis III Alpha/Beta. Leroy JG, Cathey SS, Friez MJ. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.
2008 Aug 26 [updated 2009 Jul 07]. PMID: 20301730