Salla disease (SD) or mild Free Sialic Acid Storage Disease (FSASD) is an

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 allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosome ...

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 ...

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 ...

characterized by early physical impairment and

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

. Salla disease (also referred to as Finnish-type sialuria, OMIM#604369) was first reported as a lysosomal storage disorder in a family from northern Finland. Salla refers to the area where the affected family resided. It was first described in 1979, after

Salla Salla, known as Kuolajärvi until 1936, is a municipality of Finland, located in Lapland. The municipality has a population of () and covers an area of of which is water. The population density is . The nearby settlement of Sallatunturi is ...

, a municipality in

Finnish Lapland Lapland is the largest and northernmost Regions of Finland, region of Finland. The 21 municipalities in the region cooperate in a Regional Council. Lapland borders the Finnish region of North Ostrobothnia in the south. It also borders the Gul ...

and is one of 40 Finnish heritage diseases. The term Salla disease is now used in the literature not only for FSASD cases with the Finnish founder variant in ''SLC17A5'', but also for any mild FSASD cases, independent of the mutation or region of origin. FSASD (Salla and Infantile Free Sialic Acid Storage Disease) affects males and females in equal numbers. The worldwide prevalence of FSASD is estimated at less than 1 per 1,000,000 individuals. Higher estimated prevalence rates occur in the Salla region of Finland and other Scandinavian countries.

Signs and symptoms

Affected infants appear normal at birth but may develop symptoms during the first year of life. Individuals with Salla disease may present with

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...

as well as

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 it is a potential manifestation of many different dis ...

, and may have difficulty coordinating voluntary movements (

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

), reduced muscle tone and strength, and cognitive impairment. The most severely impaired children do not walk or acquire language, but the typical patient learns to walk and speak and has normal life expectancy. The

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

shows arrested or delayed

myelination Myelination, or myelinogenesis, is the formation and development of myelin sheaths in the nervous system, typically initiated in late prenatal neurodevelopment and continuing throughout postnatal development. The term ''myelinogenesis'' is also ...

. Approximately two-thirds of children with mild FSASD eventually learn to walk. Some degree of speech impairment is usually present. Affected infants may learn single words or small sentences, but this ability may be lost as they age. The ability to produce speech is affected more severely than the ability to understand speech. Affected children exhibit some degree of cognitive impairment as well. FSASD (Salla and Infantile Free Sialic Acid Storage Disease) affects males and females in equal numbers. The worldwide prevalence of FSASD is estimated at less than 1 per 1,000,000 individuals. Higher estimated prevalence rates occur in the Salla region of Finland and other Scandinavian countries. Approximately ~300 individuals with FSASD have been reported in the literature, of which the majority (''>'' 160 cases) are of Finnish or Swedish ancestry. Individuals with FSASD may be misdiagnosed or undiagnosed, making it difficult to determine the true frequency of the disease in the general population.

Genetics

SD is caused by a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

in the SLC17A5 gene, located at human

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

6q14-15. This gene codes for

sialin Sialin, also known as H(+)/nitrate cotransporter and H(+)/sialic acid cotransporter, is a protein which in humans is encoded by the ''SLC17A5'' gene. Clinical significance A deficiency of this protein causes Salla disease. and Infantile Sial ...

, a lysosomal membrane protein that transports the charged sugar, N-acetylneuraminic acid (sialic acid), out of

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

s. The mutation causes

sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" () was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is ''N''-acetylneuraminic acid ...

to build up in the cells. The disease is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an

autosome 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 allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...

(chromosome 6 is an autosome), and two copies of the defective gene (one inherited from each parent) are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Diagnosis

A diagnosis of this disorder can be made by measuring urine to look for elevated levels of free sialic acid.

Prenatal testing Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problem ...

is also available for known carriers of this disorder. The diagnosis is ultimately confirmed by identifying genetic mutation(s) in the ''SLC17A5'' gene by molecular genetic testing. This testing is available on a clinical basis.

Treatment

There is no cure for Salla disease. Treatment is limited to controlling the symptoms of this disorder. Anti-convulsant medication may control

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

episodes. Physical therapists can assist an affected individual in building muscle strength and coordination. Genetic counseling is recommended for affected individuals and their families. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government website.https://www.clinicaltrials.gov www.clinicaltrials.gov

Prognosis

Some individuals with mild FSASD may not develop symptoms until later in childhood when a variety of neurological findings become apparent. These include

s, involuntary muscle spasms that result in slow, stiff movements of the legs (

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

), and repetitive, involuntary, writhing movements of the arms and legs ( athetosis). Some individuals who previously developed the ability to walk or talk may lose these skills (regression). Some individuals may experience a gradual coarsening of facial features.

References

External links

GeneReview/NIH/UW entry on Free Sialic Acid Storage Disorders
{{Solute carrier disorders Autosomal recessive disorders Rare diseases Glycoprotein metabolism disorders Membrane transport protein disorders