Sialic Acid Storage Disease

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The sialic acid storage disease , also Neuraminsäurespeicherkrankheit called, is a very rare autosomal - recessive inherited lysosomal storage disease .

In clinical practice, a distinction is made between two forms of sialic acid storage disease:

  • the infantile form, referred to in the Anglo-Saxon literature as infantile sialic acid storage disease (ISSD)
  • , mostly as the adult form Salla disease called

genetics

The SLC17A5 gene responsible for sialic acid storage disease is located on chromosome 6 gene locus q14-q15. The SLC17A5 gene codes for the protein sialin ; an anion / sugar transporter, which is essentially found in the lysosome or the lysosome membrane of the cells. Mutations in the SLC17A5 gene can lead to a functionally impaired gene product sialin.

pathology

After the enzymatic breakdown of the glycoproteins , glycosaminoglycans and glycolipids , the resulting monosaccharides must be transported out of the lysosome . The free sialic acids (also called neuraminic acid) are normally removed from the lysosome via anion transporters . A defect in the sialin anion transporter leads to an accumulation (storage) of sialic acid in the lysosome and thus to sialic acid storage disease.

Infantile form

In the infantile form of sialic acid storage disease, the affected patients usually have rough facial features, an enlarged liver and spleen ( hepatosplenomegaly ), and ataxia and are mentally retarded. Frequently in which prenatal a hydrops fetalis (fluid over large parts of the unborn child) by sonography (ultrasound diagnostics) detected. The prognosis of the infantile form is extremely unfavorable. The affected children usually die in the first few years of life. The incidence is around 1 per 500,000 live births worldwide.

Adult form (Salla disease)

The first symptoms of Salla disease usually appear in infancy. These are hypotension and horizontal nystagmus . Later develop spasticity . The affected patients are mentally handicapped and mostly lack the ability to speak. Most patients reach adulthood.

Demarcation

Sialuria , also called Nonaka myopathy, must be distinguished from both forms of sialic acid storage disease . In this disease, mutations in the UDP-GlcNac-2-epimerase gene lead to the failure of a control loop, which leads to the excess production and excretion of sialic acid.

Diagnosis

Like all patients with glycoprotein storage disease, patients with sialic acid storage disease excrete more oligosaccharides. In addition, an increased sialic acid concentration can be measured in the urine of the patient. The enzyme defect can be demonstrated on fibroblasts or leukocytes. A gene analysis offers complete diagnostic certainty.

therapy

There is no known specific therapy for sialic acid storage disease. Treatment is symptomatic.

Individual evidence

  1. ↑ J. Schleutker include: Lysosomal free sialic acid storage disorders with different phenotypic presentations - infantile sialic acid storage disease-form and Salla disease - represent allelic disorders on 6q14-15. In: Am. J. Hum. Genet. 57, 1995, pp. 893-901. PMID 7573051
  2. ↑ P. Leppanen et al .: A physical map of the 6q14-q15 region harboring the locus for the lysosomal membrane sialic acid transport defect. In: Genomics 37, 1996, pp. 62-67. PMID 8921371
  3. ↑ FW Verheijen et al .: A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. In: Nature Genet 23, 1999, pp. 462-465. PMID 10581036
  4. ↑ a b c d e f G. F. Hoffmann: Metabolic diseases in neurology. Georg Thieme Verlag, 2004, pp. 60–62. ISBN 3-131-36321-5
  5. ^ R. Seppala et al.: Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. In: Am J Hum Genet 64, 1999, 1563-1569. PMID 10330343

literature

  • T. Marquardt: Congenital glycosylation disorders. In: Pediatrie Springer Verlag, 2007, pp. 319–322. ISBN 978-3-540-71895-6
  • P. Aula et al: "Salla disease": a new lysosomal storage disorder. In: Arch. Neurol. 36, 1979, pp. 88-94. PMID 420628

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