α- N -acetylgalactosaminidase deficiency

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Classification according to ICD-10
E74.2 Galactose metabolism disorders
ICD-10 online (WHO version 2019)

α- N -Acetylgalactosaminidase deficiency is an extremely rare autosomal - recessive inherited lysosomal storage disease . In the juvenile form the disease is known as Schindler's disease and in the adult form as Kanzaki's disease . In some publications, the juvenile form is also referred to as Schindler's disease type I and the adult form as Schindler's disease type II . An intermediate mixed form of both diseases is called Schindler's disease type III . All three diseases are assigned to the oligosaccharidoses .

Etiology and prevalence

In the patients affected by Schindler's disease , the enzyme α- N -acetylgalactosaminidase is reduced in its activity. The cause of the enzyme defect are nonsense - or missense - mutations on the gene coding for α- N -acetylgalactosaminidase ( NAGA gene ), which is located on chromosome 22 gene locus q11. The enzyme catalyzes the cleavage of N- acetylgalactosamine from various glycoproteins and glycolipids. The decrease in enzyme activity caused by the genetic defect leads to an accumulation of the unmetabolized substances in the cells. This is essentially N - or O -verlinkte glycoproteins , glycosphingolipids and proteoglycans , the α- N -acetylgalactosamine groups have bonded terminally. These accumulations lead to damage in the cell and the affected organs.

The α- N -acetylgalactosaminidase deficiency is an extremely rare disease, the exact prevalence of which is unknown. To date, around twelve patients from a total of eight families have been described worldwide.

Symptoms and diagnostics

In Schindler's disease type I, the disease is characterized by progressive muscle hypotension in the first year of life . In addition, there are disorders in the movement sequence ( extrapyramidal syndrome ), rapid psychomotor regression, myoclonic cerebral seizures , spastic tetraplegia and blindness . Symptoms similar to Fabry disease are observed in the adult form . Those affected have angiokeratomas and little mental retardation. The intermediate form (Schindler's disease type III) manifests itself in behavioral disorders, cerebral seizures and psychomotor retardation.

The α- N -acetylgalactosaminidase deficiency can be diagnosed by the chromatographic detection of the oligosaccharides in the urine . The activity of α- N -acetylgalactosaminidase in leukocytes , fibroblasts or trophoblast tissue can also be determined in the laboratory . A DNA analysis is possible, but usually not necessary.

therapy

There is currently no specific therapy for Schindler's disease. Treatment is symptomatic.

Initial description

The α- N -acetylgalactosaminidase deficiency was first described in 1988 by the Würzburg human geneticist Detlev Schindler . He is the namesake for Schindler's disease. T. Kanzaki - namesake for Kanzaki's disease - first described the symptoms of the adult form of α- N- galactosaminidase deficiency in a 46-year-old Japanese woman in 1989 . Two years later he recognized the α- N -galactosaminidase deficiency as the cause .

Individual evidence

  1. ↑ unknown: Neuroaxonal Dystrophy. In: Functional Ultrastructure Verlag Springer, 2005, ISBN 978-3-211-83564-7 , pp. 296-297.
  2. ↑ D. Schindler et al.: Characterization of alpha-N-acetylgalactosaminidase deficiency: a new neurodegenerative lysosomal disease. In: Pediat. Res. 23, 1988, p. 333A.
  3. ↑ D. Schindler et al: Neuroaxonal dystrophy due to lysosomal alpha-N-acetyl-galactosaminidase deficiency. In: NEJM 320, 1989, pp. 1745-1740.
  4. ↑ T. Kanzaki et al.: Novel lysosomal glycoaminoacid storage disease with angiokeratoma corporis diffusum. In: The Lancet 1, 1989, pp. 875-876. PMID 2564952
  5. ↑ T. Kanzaki et al.: Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria. In: J. Clin. Invest. 88, 1991, pp. 707-711. PMID 1907616

literature

  • RJ Desnick and AM Wang: Schindler disease: An inherited neuroaxonal dystrophy due to α-N-acetylgalactosaminidase. In: Journal of Inherited Metabolic Disease 13, 1990, pp. 549-559. PMID 2122121
  • RJ Desnick and D. Schindler: α-N-acetylgalactosaminidase deficiency: Schindler's disease. In: The metabolic and molecular bases of inherited disease , McGraw-Hill, 2001, pp. 3483-3505.
  • D. Wolfe et al .: Neuroaxonal dystrophy in infantile α-N-acetylgalactosaminidase deficiency. In: J Neurol Sci 132, 1995, pp. 44-56. PMID 8523030
  • J. Rudolf et al .: Cerebral glucose metabolism in type I alpha-N-acetylgalactosaminidase deficiency: an infantile neuroaxonal dystrophy. In: J Child Neurol 14, 1999, pp. 543-547. PMID 10456768
  • RJ Desnick and AM Wang: Structural organization and complete sequence of the human alpha-N-acetylgalactosaminidase gene: homology with the alpha-galactosidase A gene provides evidence for evolution from a common ancestral gene. In: Genomics 10, 1991, pp. 133-142. PMID 1646157
  • AM Wang et al .: Human alpha-N-acetylgalactosaminidase-molecular cloning, nucleotide sequence, and expression of a full-length cDNA. Homology with human alpha-galactosidase A suggests evolution from a common ancestral gene. In: J Biol Chem 265, 1990, pp. 21859-21766 PMID 2174888
  • AM Wang et al .: Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. In: J Clin Invest 86, 1990, pp. 1752-1756. PMID 2243144

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