The mucolipidoses (ML) are a group of inherited metabolic diseases that affect the body’s ability to carry out the normal turnover of various materials within cells. In ML, abnormal amounts of carbohydrates and fatty materials (lipids) accumulate in cells. Because our cells are not able to handle such large amounts of these substances, damage to the cells occurs, causing symptoms that range from mild learning disabilities to severe intellectual impairment and skeletal deformities.
Symptoms of ML can be congenital (present at birth) or begin in early childhood or adolescence. Early symptoms can include vision problems and developmental delays. Over time, many children with ML develop poor mental capacities, have difficulty reaching normal developmental milestones, and, in many cases, eventually die of the disease.
Patients with ML are born with a genetic defect in which their bodies either do not produce enough enzymes or, in some instances, produce ineffective forms of enzymes. Without functioning enzymes, which are proteins, lysosomes cannot break down carbohydrates and lipids and transport them to their normal destination. The molecules then accumulate in the cells of various tissues in the body, leading to damage of organs. In patients with ML, the molecules accumulate in nerve, liver, and muscle tissue as well as in bone marrow, and this abnormal storage causes the various symptoms associated with ML. For example, excess storage of these molecules in nerve tissues can cause mental retardation, accumulation in the tissues of the spleen and liver can cause poor functioning of these vital organs, and excess storage in the bone marrow can damage bones, leading to skeletal deformities.
The MLs are similar to another group of lysosomal storage diseases known as the mucopolysaccharidoses. While both conditions produce similar symptoms and are caused by the lack of enzymes necessary to break down and transport carbohydrates and lipids, the mucopolysaccharidoses result in an excess of sugars, known as mucopolysaccharides, in the urine. Mucopolysaccharides are not seen in urine of patients with ML, therefore screening of the urine can help doctors distinguish between the two groups of disorders.
There are four types of ML and each is classified according to the enzyme(s) or other protein that is deficient or mutated (altered). Symptoms can range from mild to severe.
Mucolipidosis type IV (ML IV) is caused by harmful alterations of a protein in the cell that is believed to be involved in the movement of molecules such as calcium across cell membranes. Many cells throughout the body are filled with granules.
The symptoms linked to mucolipidosis IV are:
- Delay of movement development and coordination, similar to that of cerebral palsey
- Mental retardation (children generally reach a maximum developmental age of about 15 months in language and motor function; receptive ability is more than expressive ability
- Hypotonia (low muscle tone) and tendon reflexes are generally spastic
- Clouding of the cornea of the eye, and severely reduced vision
- Progressive degeneration of the retina causing severe visual disability and blindness after adolescence
- Pseudo-strabismus (false appearance of having crossed eyes)
- Unsteady gait and do not walk independently
- Brain MRI typically shows a thinner corpus callosum and a delay in the development of the white matter of the brain (myelination)
- Speech is usually severely impaired
- Achlorhydria (reduction of secretion of acid by the stomach)
- Anemia (iron deficiency)
- Increase of gastrin in the blood
ML4 individuals typically live to adult age although it is believed that their life expectancy is reduced in comparison with that of healthy adults.
The mucolipidoses are inherited in an autosomal recessive manner. If both parents care carriers, each child will have a 25% probability of inheriting the disease, a 50% chance of being an asymptomatic carrier and a 25% probability of being not affected by the disease (not even as a carrier).
Te best time to determine the genetic risk, clarify the carrier possibility and to have a discussion about the availability of prenatal testing is before pregnancy. Future parents can be tested for ML4 by a simple blood test. If both parents are ML4 carriers or carriers of any other genetic disease, they should talk with a genetic consultant. About 1 in 100 of affected individuals has Ashkenazi Jew ancestry.
Once a woman is pregnant and both parents are identified as carriers, amniocentesis can be carried out at about 18 weeks of gestation.
Gene or region studied