Mucolipidosis II and III
ML-II and ML-III are both caused by a deficiency of an enzyme (N-acetylglucosamine-1-phosphotransferase) that is needed to process other enzymes and allow them to be “targeted” to the lysosome where they can perform their function in breaking down mucopolysaccharides, complex fats and other substances. As a result of this deficit, there is a secondary deficiency of multiple enzymes in both ML-II and ML-III. This leads to the storage of sugars and fats, resulting in many health problems. A wide range of severity can be observed.
Forms of the disorders
ML-II and ML-III represent the two extremes of the ML continuum. ML-II is the severe form, and ML-III is the mild form. Individuals may present with symptoms that are in between the two forms. Due to the fact that ML disorders are rare, their projected frequency rates are not always exact. The most recent estimation is 1 in 325,000 births for both ML-II and ML-III combined.
ML-II is also referred to as I-cell disease because the resulting buildup of the excess molecules accumulates into what are called “inclusion bodies.” In the past, ML-III was referred to as pseudo-Hurler polydystrophy because researchers believed that ML-III resembled a mild form of Hurler syndrome (MPS IH).
Clinical features
Individuals with I-cell disease will usually begin to display symptoms at birth or shortly thereafter. These symptoms may include short stature, stiff “claw-like” hands, kyphosis (curvature of the spine causing a “lump on the back”), genu valgum (knock-knees), coarse facial features, gingival hyperplasia (overgrowth of the gums), corneal clouding, organomegaly (enlarged organs), hernias, repeated respiratory infections, heart problems and developmental delay. Lifespan is typically shortened.
Symptoms of ML-III are usually noted in individuals between 2 and 4 years of age. These symptoms may include relatively short stature, stiff joints, coarse facial features, problems with the valves of the heart and corneal clouding. Intelligence can be normal, but some individuals may have learning disabilities. Many of the features of ML-II can be present in ML-III, but are less severe.
Genetics of the disorders
ML-II and ML-III are inherited as autosomal recessive traits. Here's how that works: All individuals have two copies of the specific ML-II and ML-III genes and usually both function normally. However, children with ML-II or ML-III have alterations in both copies of their genes so that neither gene copy works properly. Children receive one copy of the altered gene from their mother and one copy of the altered gene from their father. The parents are not affected with the condition because they have one normal copy of the gene paired with one altered copy of the gene. The normal gene produces enough of the specific enzymes to prevent the disorder. This is referred to as being a carrier for the condition. Parents who are carriers have a 25% chance with each pregnancy to have an affected child. In turn, parents who are carriers have a 75% chance with each pregnancy to have an unaffected child. More here about autosomal recessive inheritance.
Treatment
Despite the fact that there is no cure for ML, several therapies do exist to treat the symptoms of the disorders. Possible therapies include stem cell transplantation and intravenous treatment with pamidronate. Pamidronate adheres to the bone to prevent the break down of bone tissue. The goal of this treatment is to decrease bone pain and to increase mobility. Management of the disorder also involves symptomatic treatment of specific complications that can arise in a patient with ML-II or ML-III.