Free Sialic Acid Storage Disorders: SLC17A5 Gene Sequencing
Condition Description
The disorders of free sialic acid metabolism are autosomal recessive neurodegenerative disorders that result from the buildup of free sialic acid in the lysosome due to a defective lysosomal transport protein, sialin.
They are a spectrum of disorders but two distinct phenotypes have been described. Salla disease, also known as Finnish type sialuria, is on the milder end of the spectrum. It is characterized by neurologic findings at birth that are slowly progressive, leading to mild to moderate psychomotor delays, athetosis, seizures, and spasticity in adulthood. Truncal ataxia and hypotonia typically manifest at about one year of age. Affected individuals appear normal at birth but coarse facial features may develop in adulthood. Infantile free sialic acid storage disease (ISSD) is on the more severe end of the spectrum. It is characterized by severe developmental delay, hepatosplenomegaly, cardiomegaly, and coarse facial features. Death usually occurs in early childhood. Variable expressivity has been observed within families.
Mutations in the SLC17A5 gene (6q13) cause free sialic acid storage disorders. A founder mutation for Salla disease has been described in the Finnish population. Sequence analysis of the entire SLC17A5 gene coding region is available for individuals suspected of having a disorder of free sialic acid metabolism and their at-risk relatives on a clinical basis.
References:
They are a spectrum of disorders but two distinct phenotypes have been described. Salla disease, also known as Finnish type sialuria, is on the milder end of the spectrum. It is characterized by neurologic findings at birth that are slowly progressive, leading to mild to moderate psychomotor delays, athetosis, seizures, and spasticity in adulthood. Truncal ataxia and hypotonia typically manifest at about one year of age. Affected individuals appear normal at birth but coarse facial features may develop in adulthood. Infantile free sialic acid storage disease (ISSD) is on the more severe end of the spectrum. It is characterized by severe developmental delay, hepatosplenomegaly, cardiomegaly, and coarse facial features. Death usually occurs in early childhood. Variable expressivity has been observed within families.
Mutations in the SLC17A5 gene (6q13) cause free sialic acid storage disorders. A founder mutation for Salla disease has been described in the Finnish population. Sequence analysis of the entire SLC17A5 gene coding region is available for individuals suspected of having a disorder of free sialic acid metabolism and their at-risk relatives on a clinical basis.
References:
- GeneReviews
- OMIM #604322: SLC17A5 gene
- OMIM #604369: Salla disease
- OMIM #269920: ISSD
Genes (1)
Indications
This test is indicated for:
- Confirmation of a clinical diagnosis of free sialic acid storage disorders.
- Carrier testing in adults with a family history of free sialic acid storage disorders.
Methodology
PCR amplification of 11 exons contained in the SLC17A5 gene is
performed on the patient's genomic DNA. Direct sequencing of
amplification products is performed in both forward and reverse
directions, using automated fluorescence dideoxy sequencing methods. The
patient's gene sequences are then compared to a normal reference
sequence. Sequence variations are classified as mutations, benign
variants unrelated to disease, or variations of unknown clinical
significance. Variants of unknown clinical significance may require
further studies of the patient and/or family members. This assay does
not interrogate the promoter region, deep intronic regions, or other
regulatory elements, and does not detect large deletions.
Detection
Clinical Sensitivity: Unknown. The detection rate in the Finnish population is 91% due to a founder mutation. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.
Analytical Sensitivity: ~99%
Analytical Sensitivity: ~99%
Specimen Requirements
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube:Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Special Instructions
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
Related Tests
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.