Sialic acid storage disease?
Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with this disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms
infantile free sialic acid storage disease?
Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood.
Salla disease is a less severe form of sialic acid storage disease. Babies with this disorder usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood.
Intermediate severe Salla disease (ISSD?
Intermediate severe Salla disease (ISSD Mutations in the ARSA or PSAP genes result in a decreased ability to break down sulfatides, resulting in the accumulation of these substances in cells. Excess sulfatides are toxic to the nervous system. The accumulation gradually destroys myelin-producing cells, leading to the impairment of nervous system function that occurs in metachromatic leukodystrophy. In some cases, individuals with very low arylsulfatase A activity show no symptoms of metachromatic leukodystrophy. This condition is called pseudoarylsulfatase deficiency.
What genes are related to Sialic acid storage disorder?
Mutations in the SLC17A5 genecauses all forms of sialic acid storage disease. This gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials. Sialin moves a molecule called free sialic acid, which is produced when certain proteins and fats are broken down, out of the lysosomes to other parts of the cell. Free sialic acid means that the sialic acid is not attached (bound) to other molecules.
There is currently no treatment or cure for MLD. Children with advanced juvenile or adult onset and late infantile patients displaying symptoms receive treatment limited to pain and symptom management. Presymptomatic late infantile MLD patients, as well as those with juvenile or adult MLD that are either presymptomatic or displaying mild to moderate symptoms, have the option of bone marrow transplantation (including stem cell transplantation), which is under investigation to see if it may slow down progression of the disease or stop its progression in the central nervous system. However, results in the peripheral nervous system have been less dramatic, and the long-term results of these therapies have been mixed. Recent success has involved stem cells being taken from the bone marrow of children with the disorder and infecting the cells with a retro-virus, replacing the stem cells mutated gene with the repaired gene before re-injecting it back into the patient where they multiplied. The children by the age of five where all in good condition and going to kindergarten when normally by this age, children with the disease can not even speak. Several future treatment options are currently being investigated. These include gene therapy, enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and potentially enzyme enhancement therapy (EET). A team of international researchers and foundations gathered in 2008 to form an international MLD Registry to create and manage a shared repository of knowledge, including the natural history of MLD. This consortium consisted of scientific, academic and industry resources. This registry never became operational.
How do people inherit sialic acid storage disorder-
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition
A diagnosis can be made by measuring cultured tissue samples for increased levels of free sialic acid. Prenatal testing is also available for known carriers of this disorder
There is no treatment for ISSD. Treatment is limited to controlling the symptoms of this disorder such as administering anti-convulsant medication to control seizure episodes
Who to contact for more information?
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Dr Seema Kapoor
Maulana Azad Medical College, New Delhi