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Disease Profile

Free sialic acid storage disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E77.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Sialic acid storage disease; N-Acetylneuraminic acid storage disease (former); NANA storage disease (former);

Categories

Congenital and Genetic Diseases

Summary

Free sialic acid storage diseases are inherited conditions that lead to progressive neurological damage. There are three forms of free sialic acid storage diseases; an infantile form, an intermediate severe form and Salla disease. The infantile form is the most severe, with symptoms appearing before birth or soon after. Salla disease is the least severe with symptoms that start in the first year of life and progress slowly through adulthood. The intermediate severe form is less severe than the infantile form, but more severe than Salla disease.[1][2]

General symptoms of free sialic acid storage diseases include developmental delay, low muscle tone, abnormal movements, and seizures. They are progressive, and symptoms get worse over time. All forms of free sialic acid storage disease are caused by genetic changes (mutations) in the SLC17A5 gene and are inherited in an autosomal recessive manner.[3] Free sialic acid storage disease can be diagnosed by laboratory tests looking for sialic acid in the urine, imaging studies of the brain, and genetic testing. Treatment is based on the symptoms and maintaining quality of life. People with the least severe form of this disease (Salla disease) can live into adulthood.[1][2]

Symptoms

The symptoms of free sialic acid storage disease 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 free sialic acid storage disease will have the same symptoms.

Infants with the most severe form of free sialic acid storage disease have symptoms that usually appear before or at the time of birth. The signs and symptoms of infantile free sialic acid storage disease include:[1][2][4]

Abnormal fluid buildup before birth (hydrops fetalis)
Fluid in the stomach (ascites)
Low muscle tone (hypotonia)
Enlarged liver and spleen (hepatosplenomegaly)
Coarse facial features 
Seizures
Failure to gain weight
Severe developmental delay and intellectual impairment
Bone abnormalities 
Enlarged heart (cardiomegaly)
Kidney damage

The symptoms of Salla disease, the least severe form of free sialic acid storage disease, usually appear in the first year of life and may include:[1][2][4]

Low muscle tone (hypotonia)
Developmental delay and intellectual impairment
Seizures
Abnormal movements
-Uncontrolled or uncoordinated movements (ataxia)
-Stiff or rigid muscles (spasticity)
-Involuntary, writhing movement (athetosis)
Some coarsening of facial features 
Loss of motor and speech skills 

Very few people have been diagnosed with the intermediate severe form of free sialic acid storage disease. The severity of the signs and symptoms of this condition tend to fall between the other two forms.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal foot morphology
Abnormal feet structure
Abnormality of the feet
Abnormality of the foot
Foot deformities
Foot deformity

[ more ]

0001760
Abnormal pyramidal sign
0007256
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles

[ more ]

0010318
Ataxia
0001251
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Muscular hypotonia
Low or weak muscle tone
0001252
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
30%-79% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Abnormality of skin pigmentation
Abnormal pigmentation
Abnormal skin color
Abnormal skin pigmentation
Abnormality of pigmentation
Pigmentary changes
Pigmentary skin changes
Pigmentation anomaly

[ more ]

0001000
Abnormality of the upper limb
0002817
Ascites
Accumulation of fluid in the abdomen
0001541
Athetosis
Involuntary writhing movements in fingers, hands, toes, and feet
0002305
Dysarthria
Difficulty articulating speech
0001260
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Hydrops fetalis
0001789
Iris hypopigmentation
Light eye color
0007730
Oculomotor apraxia
0000657
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Reduced bone mineral density
Low solidness and mass of the bones
0004349
Seizure
0001250
Skeletal dysplasia
0002652
Skin ulcer
Open skin sore
0200042
5%-29% of people have these symptoms
Hepatomegaly
Enlarged liver
0002240
Nephrotic syndrome
0000100
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
Splenomegaly
Increased spleen size
0001744

Cause

Free sialic acid storage diseases are caused by genetic changes in the SLC17A5 gene.[3] The specific change in the gene determines the severity of the disease.[2]

Diagnosis

Free sialic acid storage diseases are diagnosed based on the symptoms. When these conditions are suspected, the diagnosis is made through laboratory testing to look for high levels of free sialic acid in urine, as well as imaging studies to look for abnormalities in the brain. Genetic testing is also helpful and can help tell between the Salla disease and the more severe forms.[1][2]

Treatment

There is no specific treatment for the free sialic acid storage diseases. Treatment is focused on specific symptoms and on providing comfort and support for patients and their families.[1]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus Genetics contains information on Free sialic acid storage disease. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
      • The Salla Treatment and Research Foundation offers a description of Salla disease and features stories of children living with this rare condition.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Free sialic acid storage disease. Click on the link to view a sample search on this topic.

          References

          1. Adams D, Gahl WA. Free Sialic Acid Storage Disorders. GeneReviews. Updated June 6, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1470/.
          2. Free Sialic Acid Storage Disorders. National Organization for Rare Disorders (NORD). Updated 2016; https://rarediseases.org/rare-diseases/lysosomal-free-sialic-acid-storage-disorders/.
          3. Sialic acid storage disease. Genetics Home Reference. February 2008; https://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease.
          4. Barmherzig R, Bullivant G, Cordeiro D, Sinasac DS, Blaser S, Mercimek-Mahmutoglu S. A new patient with intermediate severe Salla disease with hypomyelination: A literature review for Salla disease.. Pediatr Neurol. Sept 2017; 74:87-91.e2. https//www.ncbi.nlm.nih.gov/pubmed/28662915.

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