Mucolipidosis type III




Mucolipidosis (ML) III, also called as Pseudo-Hurler polydystrophy, a rare inherited biochemical disorder involving the progressive accumulation of certain chemicals (glycoproteins and glycolipids) in body tissues due to deficiency of an enzyme (UDP-N-acetylglucosamine-I-phosphotransferase) needed to process it. Mucolipidosis III is a slowly progressive disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3 or 4, but some children are not diagnosed until later on in life.


  • Mild liver and spleen enlargement
  • Aortic valve disease
  • Joint stiffness
  • Cloudy corneas
  • Carpal tunnel syndrome
  • Skeletal deformities
  • Hyperopic astigmatism
  • Mild retinopathy


Mucolipidosis III alpha/beta is caused by mutation in the gene encoding the alpha/beta-subunits precursor gene of N-acetylglucosamine-1-phosphotransferase (GNPTAB). A mucolipidosis III variant, ML III gamma is caused by mutations in the gene encoding the gamma subunit, GNPTG. N-acetylglucosamine-1-phosphotransferase is involved in the process of attaching a molecule called mannose-6-phosphate (M6P) to specific digestive enzymes. M6P acts as a tag that indicates a digestive enzyme should be transported to the lysosome. Reduced activity of GlcNAc-1-phosphotransferase disrupt the tagging of digestive enzymes with M6P, which prevents many enzymes from reaching the lysosomes. The shortage of digestive enzymes within lysosomes causes large molecules to accumulate there.


The diagnosis of ML is based on clinical symptoms, a complete medical history, and certain laboratory tests. Diagnosis of ML III can be confirmed by a blood test that measures enzyme activity in the patient's white blood cells. Activity levels that are lower than normal indicate specific enzyme deficiencies.

Another way to confirm the diagnosis is through skin biopsy. A small sample of skin is taken from the patient and grown in a cell culture. The activity of a particular enzyme in the cultured skin cells is then measured.

Prenatal diagnosis for ML is accomplished using a procedure known as chorionic villus sampling, or CVS. It is usually done around the 8th or 10th week of pregnancy and involves removing and testing a very small sample of the placenta. For ML types III, placental cells called amniocytes are grown in culture and then tested to measure enzyme activity levels.


Patients with ML III are generally of normal intelligence or have only mild cognitive problems. Some individuals with ML III survive until their fourth or fifth decade of life.


No cure or specific therapies for ML currently exists. Therapies are generally geared toward treating symptoms and providing supportive care to the child. For individuals with corneal clouding, surgery to remove the thin layer over the eye has been shown to reduce the cloudiness in the eye. However, this improvement may be only temporary. Physical and occupational therapy may help children with motor delays. Children with language delays may benefit from speech therapy. Respiratory infections should be treated immediately and fully with antibiotics.