Free Sialic Acid Storage Disease

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. Normally fats and proteins are broken down and they produce a molecule called free sialic acid. Free sialic acid is moved out of the lysosome by an enzyme called sialin. In people with SASDs sialin is not produced or does not function normally which results in the build-up of free sialic acid in the lysosomes. The build-up causes the specific signs and symptoms of free SASDs. Babies may show little sign of the disease, but symptoms start to appear as more and more cells become damaged by the accumulation of free sialic acid.

SASDs have been classified into three major types based on severity of symptoms. Symptoms can vary greatly but all forms share features of brain related impairment.

• Infantile free sialic acid storage disease (ISSD) is the most severe

• Intermediate Salla disease, severity of the disease is on a spectrum between ISSD and Salla disease

• Salla disease is the mildest form.

SASDs are autosomal recessive diseases 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 in our publication.

For each pregnancy the chances of a baby inheriting SASDs are completely independent of whether a previous child was affected with SASDs. With each pregnancy there is a 1 in 4 chance that the baby will be affected by SASDs.

All parents of children with SASDs 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 SASDs, screening tests can be arranged early on during a pregnancy for those families who already have a child with SASDs. 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.

Amniocentesis and chorionic villus sampling are both available during the pregnancy to find out if the baby is affected by SASDs.

It might also be possible to have Pre-implantation genetic diagnosis (PGD) screening to avoid passing SASDs to the baby. PGD is an assisted fertility treatment that involves checking the chromosomes of embryos before they are transferred in the womb using IVF techniques.

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.

SASDs are very rare, ISSD has been identified in a few dozen infants worldwide. Salla disease occurs mainly in Finland and Sweden and has been reported in approximately 150 people. A few people have been identified as having intermediate severe Salla disease. SASDs may go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population.

General symptoms of SASDs include developmental delay, low muscle tone, abnormal movements, and seizures. They are progressive which means symptoms get worse over time, and the symptoms may be different from person to person. Some people may be more severely affected than others, even people who have the same form. Not everyone with SASDs will have the same symptoms.

Infantile form

ISSD is the most severe form, with symptoms appearing before birth or soon after; some infants may be born prematurely. Some babies are born with a condition called hydrops fetalis. This is a very severe condition in which the baby retains an enormous amount of fluid throughout its body. Babies with hydrops fetalis rarely survive beyond a few weeks to a few months of age.

Babies with ISSD have severe developmental delay, weak muscle tone and failure to gain weight. They may have characteristic facial features; seizures; bone malformations (clubbed feet, abnormally short thigh bones, malformation of the hip and underdevelopment of certain bones of the fingers and toes); an enlarged liver, spleen and heart. The tummy (abdomen) may be swollen due to the enlarged organs and an abnormal build-up of fluid. ISSD eventually progresses to cause life-threatening complications such as serious respiratory infections. Some infants develop damage to the kidneys which causes them to leak large quantities of protein into the urine and can cause swelling in the body due to fluid accumulation. Children with ISSD usually live only into early childhood.

Salla disease

Salla disease is the mildest form of the SASDs with symptoms that start in the first year of life and progress slowly through adulthood. Signs and symptoms of Salla disease vary from person to person and not everyone will experience every symptom.

Babies with Salla disease usually show signs of weak muscle tone during the first year of life and go on to experience progressive symptoms of the brain. Symptoms may include gradual coarsening of facial features, intellectual disability and developmental delay, some degree of speech impairment, seizures, problems with movement and balance, abnormal tensing of the muscles, and involuntary slow movements of the limbs. Although Salla disease can cause life-threatening complications, people with Salla disease usually survive into adulthood and some have lived into their seventies.

Intermediate severe form

Very few people have been diagnosed with the intermediate severe form of SASDs. The intermediate severe form is less severe than ISSD but more severe than Salla disease. People with the intermediate severe form have signs and symptoms that fall between those of ISSD and Salla disease in severity.

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.

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.

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 offer 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.

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