Mucolipidosis III (ML III)

Mucolipidosis III (ML III) is a rare, inherited disorder that is progressive in nature and affects many of the body’s systems. It is one of many diseases classified as a lysosomal storage disorder (LSD). In these disorders, genetic variations disrupt the normal activity of lysosomes in human cells.

Lysosomes in human cells contain specific proteins known as enzymes which are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes or do not contain one of these enzymes in sufficient quantities to break down molecules for cells to function properly.

Children born with mucolipidosis III often display no signs of the disorder at birth, with symptoms typically appearing around three years of age.

Signs and symptoms a child with mucolipidosis III may experience include:

• Short stature
• Skeletal and/or joint abnormalities
• Low bone density (osteoporosis)
• Bone pain
• Distinct facial features (coarse facial features)
• Frequent ear infections
• Frequent respiratory infections
• Clouding over the clear covering of the eye (corneal clouding)
• Learning difficulties
• Mild intellectual disability
• Hoarse voice due to vocal cord stiffening

Mucolipidosis III is caused by a mutation in a gene called GNPTAB, which results reduced activity of the enzyme GlcNAc-1-phosphotransferase, which lysosomes require to properly break down large molecules inside the body’s cells. This genetic condition is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the GNPTAB gene from each of their parents.

ML III is closely related to ML II, which is also caused by a mutation in the gene GNPTAB. In the case of ML II, genetic variation results in a complete absence of GlcNAc-1-phosphotransferase, leading to a more severe disease course.

There are currently no approved therapies that reverse the effects of mucolipidosis III. Current approaches involve managing specific symptoms through targeted therapies and collaboration between specialists.

At the Boston Children’s Lysosomal Storage Disorders (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic, and by working with a broad array of world class specialists here at BCH to help optimize the management of your child’s mucolipidosis.