What are Mucolipidoses?
Mucolipidoses (ML) are a group of genetic, metabolic diseases which lead to the accumulation of abnormal amounts of lipids (fatty substances) and carbohydrates in cells. The cells are unable to handle this accumulation of waste substances and thus get damaged leading to symptoms such as cognitive impairment, physical disability and various other problems in vital organs. Many children and adults may even die due to the disease.
Mucolipidoses are classified under the Lysosomal Storage Disorders (LSDs) as it involves the unnatural storage of waste substances in the lysosomes.
The global prevalence of ML is 1 in 100,000 live births.
Lysosomes have a critical role in the body’s metabolic functions. The lysosomes pick up lipids and carbohydrates and break these into smaller molecules for the metabolic process. This process is facilitated by the lysosomal enzymes which enable the breakdown of substances which are then transported to the rest of the cell for energy production or excretion.
In patients with lysosomal storage disorders, a genetic defect in the gene producing the enzyme leads to a lack of the enzyme or a defective form of the enzyme. Without these enzymes, the lysosomes cannot break down the lipids or carbohydrates. These substances accumulate in the cells and damage the cell and consequently the organs. In patients with ML, the accumulated substances in the nerve, liver, spleen, bone marrow and muscle tissue can lead to physical deformities, weak bones and even liver failure.
There are four types of mucolipidoses based on the enzyme which is either mutated or deficient.
- Mucolipidosis type I or sialidosis – results from a deficiency in the enzyme, sialidase. Sialidase removes a form of sialic acid, a sugarlike molecule from sugar protein complexes. Since the enzyme is deficient, sugarlike substances accumulate in the bone marrow, neurons and other cells.
- Mucolipidosis type II and III – result from a deficiency of the enzyme, N-acetylglucosamine-1-phosphotransferase. In ML II and III the enzyme is supposed to tag other enzyme to facilitate the metabolic process. Since these activator proteins are not tagged properly they slip into spaces outside the cell and cannot function normally.
- Mucolipidosis type IV – is caused by mutations of a protein in the cell which is supposed to facilitate the movement of molecules like calcium across the cell membrane. Thus, the cells in the body are filled with granules.
Symptoms can be present at birth or slowly develop during childhood. Signs and symptoms of mucolipidoses depend on the type:
- ML I – infants are born with coarse facial features like a flat nasal bridge, puffy eyelids and thick tongue. Many infants are born with skeletal dysplasias and malformations. Infants often present with a red spot in the eye. Infants and children suffer from involuntary movements like ataxia. Many children present with intellectual impairment, poor muscle tone, liver and spleen enlargement, failure to thrive and recurrent respiratory infections. Many infants with ML I do not survive beyond the age of one.
- ML II and III – children with ML II present with similar symptoms including flat nasal bridge, puffy eyelids, thick tongue, poor muscle tone, liver and spleen enlargement, failure to thrive, dwarfism, delayed motor and intellectual development, respiratory and ear infections and clouding of the cornea. Many children with ML II die before the age of seven due to congestive heart failure.
- ML III presents with symptoms usually around the age of 5. Children with ML III have normal cognitive development but present with symptoms like flat nasal bridge, puffy eyelids, thick tongue, skeletal abnormalities, short height and corneal clouding.
- ML IV – children with ML IV present with delayed movement and coordination, corneal clouding, unsteady gait and inability to walk independently. In some cases, children have speech impairment and other visual issues.
If the neurologist or pediatrician suspects one of the mucolipidoses, he/she will usually take a family history and history of the person’s symptoms along with a detailed neurological examination. Some of the tests that are used to diagnose mucolipidoses include:
- blood tests which measure the activity of enzymes in the blood
- skin biopsy to measure the activity of enzyme in the skin culture
- ML IV can be tested with a conjunctival swab which checks for inclusion bodies
- genetic testing – to check for various genotypes of mucolipidoses
Currently, no specific treatment is available for mucolipidoses. Treatment is aimed at preventing complications and enabling independent living. An interdisciplinary team of doctors including pediatricians, neurologists, orthopedicians and physiotherapists will be required to take care of the clinical needs of the child/adult. In the early stages when just diagnosed, it is important to immediately start physiotherapy and rehab to prevent further deterioration and maintain a certain level of mobility.
Physiotherapy is highly recommended to preserve muscle strength. Wheelchairs may be required in some cases. Adaptive devices are also useful to perform daily tasks. Some of the devices include specialized crutches and sticks, special utensils for eating and communication aids. Other helpful therapies include occupational therapy and speech therapy.
Children and adult who develop weak bones must get adequate calcium and if necessary bisphosphonates to prevent fractures.
For children with corneal clouding, a surgery may be required to reduce the cloudiness. Children with ML must be given proper nutrition and nutritional supplements as they often fail to grow and thrive. Proper precautions must be taken to avoid respiratory infections. Vaccines to prevent pneumonia and meningitis must be given at the right time. Any suspected infection must be immediately treated with antibiotic therapy.
Children and adults with mucolipidoses must be encouraged to participate in all life activities and must be encouraged to go to regular schools, colleges and participate in social activities. Genetic counselling and psychosocial counselling must be made available whenever required with other supportive measures.
If there is a known case of ML in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.
If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.