Mucolipidoses: Group of Rare Inherited Disorders

What Are Mucolipidoses?

Mucolipidoses (ML) are a group of inherited metabolic diseases that impact the capability of the body to carry out the regular repair and regeneration of various materials within cells. In these conditions, there is an abnormal accumulation of carbohydrates and fatty substances (lipids) in the lysosomes within the body's cells. Lysosomes are parts of the cell that help process carbohydrates and lipids by breaking them down into smaller and simpler molecules with the help of enzymes.

Therefore, people with mucolipidoses either lack these or have ineffective enzymes, leading to increased cell substances. Thus, the cells cannot handle this large amount of carbohydrates and lipids, which then starts damaging the cells, and symptoms like skeletal deformities and intellectual impairment can occur.

What Are the Types of Mucolipidoses?

There are four types of mucolipidoses, sialidosis (ML I), and types II, III, and IV.

1. Mucolipidoses Type I (ML I) or Salidosis - This type of mucolipidoses occurs due to a deficiency in a digestive enzyme called sialidase. The action of sialidase is to terminate a variety of sialic acid (a sugar-like molecule) from sugar-protein complexes responsible for proper cell functioning.

The symptoms present in mucolipidoses type I are usually present at birth or evolve during the first year of life, which include -

• In many infants, there can be excessive swelling throughout the body, and these infants will also have coarse facial features such as a flat nasal bridge, enlargement of gums, and excessive tongue size (macroglossia).

• Skeletal abnormalities such as hip dislocation.

• Sudden involuntary muscle contractions (myoclonus).

• Unable to coordinate voluntary movements (ataxia).

• Moreover, tremors, seizures, and impaired vision may also be seen in some cases.

By conducting various imaging examinations, liver and spleen enlargement can be found, along with abdominal swelling. Children with this condition also have impaired intellect and weak muscle tone (hypotonia). Therefore, they suffer from failure to thrive and recurrent respiratory infections; most of them die before one year.

2. Mucolipidoses Types II (ML II) - This results from the deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase. This enzyme is responsible for the functioning of other enzymes, such as activator proteins, but instructs them to work at a specific location to start different metabolic processes in the body. Due to the absence of the enzyme N-acetylglucosamine-1-phosphotransferase, the proteins may escape into the cell's outer spaces and can metabolize other substances such as carbohydrates or fats (lipids) in the cell.

ML II is also known as an inclusion-cell disease (I-cell). In this type, the waste products, including carbohydrates, lipids, and proteins, get accumulate into masses known as inclusion bodies. Additionally, examining the body's tissues under a microscope and detecting inclusion bodies in those tissues helps identify this condition.

ML II is considered the severe form of mucolipidoses (ML), which shows some of the following signs and symptoms such as -

• Abnormal skeletal development.

• Coarse facial features.

• Restricted joint movement.

• Enlargement of the liver (hepatomegaly) or spleen (splenomegaly).

• Clouding in the cornea of the eye.

• Lack of growth leads to dwarfism (short stature due to a genetic condition).

• Recurrent infections like respiratory tract infections, otitis media (middle ear infections), and bronchitis.

Children with this condition generally die in the early stages of life due to congestive heart failure or recurrent respiratory tract infections. However, the symptoms of ML II are not noticed until the third or fifth year of life.

3. Mucolipidoses Types III (ML III) - In comparison to type II, ML III is much milder, and the symptoms of ML III are not noticed until the child is three to five years old. This type is also known as pseudo-Hurler poly dystrophy and is caused due to the defect of the same enzyme as type II, which is N-acetylglucosamine-1-phosphotransferase. However, type III causes less severe symptoms and advances very slowly.

Patients with this condition may not be intellectually impaired and only have mild cognitive problems. Some symptoms may be seen, skeletal abnormalities, coarse facial features, short height, and corneal clouding. Patients with this type can survive for many years without any complications.

4. Mucolipidoses Type IV (ML IV) - This type occurs due to the problem in the functioning of a protein that is involved in the movements of molecules such as calcium across cell membranes.

The majority of the patients with this condition have some of the following symptoms -

• Delay of movement, development, and coordination.

• Severely low vision.

• Clouding of the cornea of the eye.

• Unsteady gait and may not be able to walk independently.

• Speech may also be severely impaired.

However, some individuals may get mildly affected and not have all these symptoms.

How Are Mucolipidoses Inherited?

Mucolipidoses are genetically inherited conditions that show autosomal recessive inheritance. That means it occurs when both parents carry copies of the defective gene, and the child inherits this condition when they get both copies of the defective gene from each parent. People with only one copy of the defective gene do not have this disease but may pass on the defective gene to their children. Therefore, parents who have a child with this condition should be genetically counseled with adequate psychological support.

How Are Mucolipidoses Diagnosed?

The diagnosis of mucolipidoses is done by a healthcare provider based on the symptoms and patient history and by conducting specific laboratory tests, which include -

• Blood Test - The diagnosis of all types I, II, and III can be made by conducting a blood test through which the enzyme activity in the white blood cells and the lower levels indicates specific enzyme deficiencies. In addition, measurement of the gastrin level in the blood, which is remarkably high in ML IV patients, helps confirm the diagnosis.

• Biopsy - Another method is skin biopsy, in which a skin sample is taken and grown in cell culture, and the activity of a specific enzyme in the skin cells is measured.

Prenatal Diagnosis:

This can be done by a procedure called chorionic villus sampling or CVS. This is performed around the eighth or tenth week of pregnancy. During this procedure, a small sample of the placenta and the placental cells called amniocytes are grown in culture and are tested for enzyme activity levels. This is done for types ML I, II, and III, and for type ML IV no culture is required. DNA is obtained directly from amniocytes and can be examined for any mutation, this technique is called genotyping.

What Is the Treatment for Mucolipidoses?

There is no specific cure for mucolipidoses, and this condition can only be managed by treating the symptoms and providing supportive care to the child.

• Physical therapy can be done in children with motor functioning, such as movements.

• Speech therapy in case of language delays.

• Surgeries such as eye surgery can be done to treat cornea clouding.

The treatment aims to keep the individual healthy and functional for as long as possible. Care should be provided to maintain the patient's overall health, such as providing essential nutrients and treating respiratory infections with antibiotics.

Conclusion

Mucolipidoses is a rare inherited condition, and there is still research for a better understanding of this condition. Clinical trials are being conducted to identify this disease's potential outcomes and progression and formulate treatment plans. Therefore, the approach for managing this condition is to address specific symptoms through targeted therapies and collaboration between specialties.