Galactosialidosis

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Classification according to ICD-10
E77.8 Other disorders of glycoprotein metabolism
ICD-10 online (WHO version 2019)

Galactosialidosis (also Goldberg syndrome or neuraminidase β-galactosidase deficiency ) is a rare autosomal - recessive inherited lysosomal storage disease from the group of oligosaccharidoses .

etiology

The cause of galactosialidosis is a greatly reduced activity of the enzymes α-D- neurominidase and β-galactosidase , which is caused by a defect in the bi-functional protein Protective Protein / Cathepsin A (PPCA). Together with neuraminidase and β-galactosidase, PPCA forms a multi-enzyme complex, whereby PPCA stabilizes these two enzymes in an acidic environment and thus ensures their activity in the lysosome. The PPCA regulates intracellular transport. The β-galactosidase is stabilized by aggregation of the individual β-galactosidase units into high-molecular multimers . Mutations in the PPGB gene coding for PPCA cause a loss of function or a restriction of the function of the gene product PPCA. These are mostly missense mutations. However, abnormal splicing of the mRNA due to modification of the splice sites has been described as the cause. The affected PPGB gene is located on chromosome 20 gene locus 13.1.

Symptoms and diagnosis

In clinical practice, a distinction is made between three phenotypes of galactosialidosis:

  • the congenital or early infantile form
  • the late infantile
  • the juvenile / adult form

The congenital or early infantile form is characterized by edema , ascites , enlargement of the liver and spleen ( hepatosplenomegaly ), chronic kidney failure , various neurological symptoms (e.g. mental retardation ), deformations of the face and malformations of the skeleton . There is usually a cherry-red spot on the macula. The disease leads to early blindness . Galactosialidosis manifests itself prenatally as hydrops fetalis . Life expectancy with this phenotype is one year or less.

In the late infantile form, the psychic abilities are hardly or not at all restricted. The affected children often only reach the second decade of life.

In the juvenile / adult form, which occurs mainly in Japan , the course of the disease is slowly progressive . Deformations of the face, dysostosis multiplex and angiokeratomas are the primary symptoms here, alongside corneal opacity and the cherry-red spot in the macula. Patients with this phenotype reach adulthood.

Affected patients excrete increased amounts of oligosaccharides in the urine . These can be detected by thin-layer chromatography . The activity of the affected enzymes can be determined in fibroblasts and trophoblasts (prenatal).

Therapy and prognosis

There is currently no known causal therapy. Treatment is symptomatic.

Initial description

Galactosialidosis was first described in 1971 by the American ophthalmologist Morton F. Goldberg . Goldberg syndrome is to be differentiated from Shprintzen-Goldberg syndrome , which is another disease very similar to Marfan syndrome .

Individual evidence

  1. ↑ a b R. Kreutzer: Characterization of the genetic defect of GM1 gangliosidosis in the Alaskan Husky. Dissertation, Justus Liebig University Giessen, 2005
  2. ↑ H. Morreau et al .: Human lysosomal protective protein: glycosylation, intracellular transport, and association with beta-galactosidase in the endoplasmic reticulum. In: J. Biol. Chem. 267, 1992, pp. 17949-17956. PMID 1387645
  3. ↑ Shimmoto, among others: Protective protein gene mutations in galactosialidosis. In: J. Clin. Invest. 91, 1993, pp. 2393-2398.
  4. ↑ K. Takiguchi et al .: Structural and functional study of K453 mutant protective protein / cathepsin A causing the late infantile form of galactosialidosis. In: J. Hum. Genet. 45, 2000, pp. 200-206.
  5. ↑ J. Wiegant include: The gene encoding human protective protein (PPBG) is on chromosome 20. In: Genomics 10, 1991, pp 345-349. PMID 2071143
  6. ^ MF Goldberg et al.: Macular cherry-red spot, corneal clouding, and beta-galactosidase deficiency: clinical, biochemical, and electron microscopic study of a new autosomal recessive storage disease. In: Arch. Intern. Med. 128, 1971, pp. 387-398. PMID 4999185

literature

Reference books

  • J. Cervós-Navarro and others: Special pathological anatomy. Verlag Springer, 1991, ISBN 3-540-52873-3 , pp. 73-75.
  • GF Hoffmann: Metabolic diseases in neurology Georg Thieme Verlag, 2004, ISBN 3-13-136321-5 , pp. 54–57.

Review article

  • Y. Okamura-Oho et al .: The biochemistry and clinical features of galactosialidosis. In: Biochim Biophys Acta 1225, 1994, pp. 244-254. PMID 8312369
  • D. Landau et al: Hydrops fetalis in four siblings caused by galactosialidosis. In: Isr J Med Sci 31, 1995, pp. 321-322. PMID 7759227

Technical article

  • N. Darin, M. Kyllerman, AL Hård, C. Nordborg, JE Månsson: Juvenile galactosialidosis with attacks of neuropathic pain and absence of sialyloligosacchariduria. In: Eur. J. Pediatr. Neurol. 13, 2009, pp. 553-555, PMID 19097920 .
  • K. Koike et al .: Galactosialidosis associated with IgA nephropathy: morphological study of renal biopsy. In: Pathol Int 58, 2008, pp. 295-299. PMID 18429828
  • Y. Arai et al .: Vascular pathology in galactosialidosis. In: Ultrastruct Pathol 23, 1999, pp. 369-374. PMID 10626686
  • Y. Naganawa et al .: Stable expression of protective protein / cathepsin A-green fluorescent protein fusion genes in a fibroblastic cell line from a galactosialidosis patient. Model system for revealing the intracellular transport of normal and mutated lysosomal enzymes. In: Biochem J 340, 1999, pp. 467-474. PMID 10333491
  • P. Strisciuglio et al .: The presence of a reduced amount of 32-kd "protective" protein is a distinct biochemical finding in late infantile galactosialidosis. In: Hum Genet 80, 1988, pp. 304-306. PMID 3142815
  • K. Itoh et al: Acid carboxypeptidase deficiency in galactosialidosis. In: Jinrui Idengaku Zasshi 36, 1991, pp. 171-177. PMID 1920915
  • WJ Kleijer et al .: Cathepsin A deficiency in galactosialidosis: studies of patients and carriers in 16 families. In: Pediatr Res . 39, 1996, pp. 1067-1071. PMID 8725271

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