What are the other Names for this Condition? (Also known as/Synonyms)

• Free SASD
• Lysosomal Free Sialic Acid Storage Disorder
• Sialic Acid Storage Disease

What is Free Sialic Acid Storage Disease? (Definition/Background Information)

• Free Sialic Acid Storage Disease (Free SASD), is a group of lysosomal storage diseases characterized by a spectrum of clinical manifestations
• These include neurological and developmental disorders with severity ranging from the milder phenotype, Salla disease (SD), to the most severe phenotype, infantile free sialic acid storage disease (ISSD)

(Source: Free Sialic Acid Storage Disease; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Free Sialic Acid Storage Disease? (Age and Sex Distribution)

• Free Sialic Acid Storage Disease is a rare congenital disorder. The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Free Sialic Acid Storage Disease? (Predisposing Factors)

• A positive family history may be an important risk factor, since Free Sialic Acid Storage Disease is an inherited condition
• Currently, no other risk factors have been clearly identified for Free SASD

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Free Sialic Acid Storage Disease? (Etiology)

• Free Sialic Acid Storage Disease is caused by mutation(s) in the SLC17A5 gene
• This gene codes for the protein sialin, a member of the anion/cation symporter family
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Free Sialic Acid Storage Disease?

The signs and symptoms of Free Sialic Acid Storage Disease may vary in type and severity in affected individuals, and include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormal pyramidal sign
• Abnormality of the foot
• Aplasia/hypoplasia of the abdominal wall musculature
• Ataxia 
• Gait disturbance
• Global developmental delay 
• Intellectual disability
• Muscular hypotonia
• Nystagmus
• Spasticity

Frequently present symptoms in 30-79% of the cases:

• Abnormal facial shape
• Abnormality of skin pigmentation
• Abnormality of the upper limb 
• Ascites
• Athetosis 
• Dysarthria
• Failure to thrive in infancy
• Hydrops fetalis 
• Iris hypopigmentation 
• Oculomotor apraxia 
• Recurrent respiratory infections
• Reduced bone mineral density
• Seizures
• Skeletal dysplasia
• Skin ulcer

Occasionally present symptoms in 5-29% of the cases:

• Hepatomegaly
• Nephrotic syndrome 
• Proteinuria
• Splenomegaly

(Source: Free Sialic Acid Storage Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Free Sialic Acid Storage Disease Diagnosed?

Free Sialic Acid Storage Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests, such as presence of excessive amounts of free sialic acid in the urine
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Free Sialic Acid Storage Disease?

The complications of Free Sialic Acid Storage Disease may include:

• Severe mental retardation
• Falls and injury, if seizures are present
• Immobility
• Poor quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Free Sialic Acid Storage Disease Treated?

There is no cure for Free Sialic Acid Storage Disease, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Free Sialic Acid Storage Disease be Prevented?

Currently, Free Sialic Acid Storage Disease may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Free Sialic Acid Storage Disease? (Outcomes/Resolutions)

• The prognosis of Free Sialic Acid Storage Disease is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Free Sialic Acid Storage Disease:

Free Sialic Acid Storage Disease was earlier known by the following terms:

• N-acetylneuraminic acid storage disease
• NANA storage disease

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/