Mucolipidosis type IV (MLIV) is a rare inherited lysosomal storage disorder affecting multiple body systems. It is characterized by the abnormal accumulation of substances within cellular structures called lysosomes, leading to various physical and developmental abnormalities. Mutations in the MCOLN1 gene cause MLIV. Mucolipidoses are classified into 4 types according to the affected lysosomal enzyme. Type IV mucolipidosis is caused by a deficiency of the enzyme mucolipin-1, caused by pathogenic variants in the MCOLN1 gene and mainly affects the nervous system, producing neurodegeneration. Type IV mucolipidosis is more frequent in the Ashkenazi Jewish population, in which one in every 100 persons carries a pathogenic variant in MCOLN1.
Mucolipidosis type IV genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of mucolipidosis type IV include:
- Neurological Involvement: Mucolipidosis type IV primarily affects the nervous system, leading to developmental delay, intellectual disability, and progressive motor dysfunction.
- Psychomotor Retardation: Children with mucolipidosis type IV often experience psychomotor retardation, which refers to delays in acquiring motor and cognitive skills.
- Eye Abnormalities: MLIV is associated with distinctive eye abnormalities, including corneal clouding, retinal degeneration, and impaired vision. The corneal clouding can give the eyes a characteristic appearance.
- Hypotonia: Hypotonia, or low muscle tone, is common in individuals with mucolipidosis type IV and contributes to motor skills and coordination difficulties.
- Delayed Speech Development: Speech development is often delayed in individuals with mucolipidosis type IV, and speech may be limited.
- Joint Abnormalities: Joint abnormalities, such as contractures, may occur, limiting joint mobility.
- Growth Retardation: Individuals with mucolipidosis type IV may experience growth retardation, resulting in short stature.
- Swallowing Difficulties: Difficulties with swallowing may contribute to feeding problems.
- Visceral Organ Involvement: Mucolipidosis type IV can affect various visceral organs, leading to organomegaly (enlarged organs) and other abnormalities.
- Progressive Nature: Mucolipidosis type IV is a progressive disorder, and symptoms worsen over time.
Mucolipidosis type IV is inherited in an autosomal recessive manner, meaning that affected individuals inherit mutations in the MCOLN1 gene from both parents.
There is currently no cure for mucolipidosis type IV, and management involves supportive care to address the specific symptoms and complications. This may include physical and occupational therapy, educational support, and interventions to address vision and mobility challenges. Individuals with MLIV often require multidisciplinary care involving neurologists, ophthalmologists, and other specialists.
Genetic counseling is essential for families affected by mucolipidosis type IV to understand the risk of having affected children and to discuss family planning options.
More Information
Mucolipidosis type IV is an autosomal recessively inherited lysosomal storage disease caused by mutations in the MCOLN1 gene that codes for mucolipin-1, a membrane protein belonging to the transient potential ion channels involved in transporting fats and sugars into cells.
One of the most frequent variants is c.406-2A>G, which causes defects at the cleavage and splice site of exon 3 and alters the reading pattern, generating an aberrant non-functional protein. This variant has been observed in patients in both homozygosis and compound heterozygosis.
Mucolipidosis type IV genetic testing analyzes the 8 most frequent pathogenic mutations of the MCOLN1 gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
