Mucolipidosis Type IV
What is Mucolipidosis Type IV?
Mucolipidosis type IV (ML IV) also known as ganglioside sialidase deficiency and sialolipidosis, is an inherited lysosomal storage disease, belonging to the group of oligosaccharidosis that affects many organs and tissues, including the nervous system.
What causes Mucolipidosis Type IV?
In the course of normal life there is a continuous recycling process of building new materials and breaking down old ones ready for disposal. This activity takes place in a special part of the body’s cells called the lysosome. This process requires a series of biochemical tools called enzymes. Mucolipin-1, an enzyme, plays a role in the transport of fats (lipids) and proteins. In children with ML IV levels of mucolipin-1 are low or the absent and normal transport of fats and proteins is affected. Mucolipin-1 appears to be important for the development and maintenance of the brain and retina. Babies may show little sign of the disease, but symptoms start to appear as more and more cells become damaged by the accumulation of fats and proteins which have not been transported.
How is Mucolipidosis Type IV inherited?
ML IV is an autosomal recessive disease this means that both parents must carry the same affected gene and each pass this same affected gene to their child.
People probably carry from 5 to 10 genes with mutations in each of their cells. Problems happen when the particular gene is dominant or when a mutation is present in both copies of a recessive gene pair. Genes are the unique set of instructions inside our bodies that make each of us an individual. They are the blueprint for our growth and development, as well as controlling how our bodies function. Genes are carried on structures called chromosomes and it is usual to have 23 pairs. A child will inherit half of the chromosomes from the mother and the other half from the father resulting in 23 pairs. 22 of these pairs look the same in both males and females. Pair 23 are the sex chromosomes, and this is the pair that differ between females and males. The X chromosome is inherited from the mother and the Y chromosome is inherited from the father. More information about inheritance is available here.
For each pregnancy the chances of a baby inheriting ML IV are completely independent of whether a previous child was affected with ML IV. With each pregnancy there is a 1 in 4 chance that the baby will be affected by ML IV.
All parents of children with ML IV can benefit from genetic counselling, the counsellor can provide advice on the risk to close relatives and to suggest whether the wider family should be informed. To find out during a pregnancy, if the baby is affected by ML IV, screening tests can be arranged early on during a pregnancy for those families who already have a child with ML IV. Where only one parent is a carrier, they can opt for carrier screening but it is not 100% reliable or accurate and is not possible in all cases.
How common is Mucolipidosis Type IV?
It is estimated that nearly 6% of the UK population (around 3.5million people) will be affected by a rare disease at some point in their lives. A single rare disease may affect up to about 30,000 people however the vast majority of rare diseases affect far fewer than this.
ML IV is estimated to occur in 1 in 40,000 people, about 70% of those affected have Ashkenazi Jewish ancestry.
How are people with Mucolipidosis Type IV affected?
Approximately 95 % of those affected with this disease have the severe form. People with the severe form usually survive to adulthood; however, they may have a shortened lifespan. In the first year of life babies the common signs and symptoms are pronounced developmental delays in skills, such as sitting, standing and walking, speech and chewing. Weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness, and problems controlling hand movements. Most children with ML IV are unable to walk independently. In about 15% of affected people, intellectual disability and movement skills worsen over time.
Vision may be normal at birth in babies with ML IV, but it becomes increasingly impaired during the first decade of life. People with this condition develop clouding of the clear covering of the eye (cornea) and progressive breakdown of the light-sensitive layer at the back of the eye (retina). By their early teens people with ML IV have severe vision loss or blindness. People with typical ML IV also have impaired production of stomach acid, although this does not cause any symptoms it does result in unusually high levels of gastrin in the blood. Gastrin is a hormone that regulates the production of stomach acid. Also, some people may not have enough iron in their blood, which can lead to a shortage of red blood cells causing anaemia.
About 5% of affected people with ML IV usually have mild developmental delays and may develop the ability to walk. They tend to have milder eye abnormalities than those with the severe form of the disease.
Treatment options for people with Mucolipidosis Type IV
At present there is treatment for symptoms as they arise, but no cure for the underlying disease. More information on supportive care treatments for people with MPS and related diseases can be found in the treatments section.
Research & Clinical trials for people with Mucolipidosis Type IV
For an up-to-date list of current UK based trials taking place visit Be Part of Research (resource provided by the National Institute for Health Research). For an international search visit Clinical Trials (resource provided by the U.S. National Library of Medicine). This resource provides information on trial status including recruiting, completed or withdrawn and worldwide trial locations. To find out more about past or current trials speak to your doctor and learn about the risks and potential benefits.
Living with Mucolipidosis Type IV
The MPS Society is the only UK charity at the forefront of supporting people and families affected by MPS and related diseases. Our extensive support services offers you a wide range of support and resources. The team can advise and sign post you to adequate needs-led support and services in your local area as well as social care, home adaptions, education and much more. The support team can visit you in your home and provide you with vital support and includes an Advocacy Officer based at Belfast City Hospital supporting members in Northern Ireland.
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