Infantile free sialic acid storage disease (ISSD) is a

lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

. ISSD occurs when

sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...

is unable to be transported out of the lysosomal membrane and instead accumulates in the tissue, causing free sialic acid to be excreted in the urine. Mutations in the SLC17A5 (solute carrier family 17 (anion/sugar transporter), member 50) gene cause all forms of sialic acid storage disease. The SLC17A5 gene is located on the long (q) arm of

chromosome 6 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total ...

between positions 14 and 15. 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. ISSD is the most severe form of the sialic acid storage diseases. Babies with this condition have severe developmental delay, weak muscle tone (

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...

), and failure to gain weight and grow at the expected rate (

failure to thrive Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...

). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, enlarged liver and spleen (

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and hist ...

), and an enlarged heart (

cardiomegaly Cardiomegaly (sometimes megacardia or megalocardia) is a medical condition in which the heart is enlarged. As such, it is more commonly referred to simply as "having an enlarged heart". It is usually the result of underlying conditions that make t ...

). ISSD is a rare

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

disorder and affects 1 in 528,000 live births worldwide.

Symptoms and signs

Symptoms present by eight months of age and are marked by developmental delay followed by neurological complications such as

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

, involuntary eye movements, and

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, involuntary muscle movements and failure to gain weight and grow at the expected rate (

). Babies with this condition also have and enlarged liver and spleen (

) and enlarged heart (

Cause

Diagnosis

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

Treatment

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 An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

episodes.

References

External links

GeneReviews/NCBI/NIH/UW entry on Free Sialic Acid Storage Disorders
{{Medical resources , ICD10 = E77.8 , ICD9 = , ICDO = , OMIM = 269920 , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 309324 Rare diseases Autosomal recessive disorders