Sialolipidosis

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Classification according to ICD-10
E75.1 Other gangliosidoses
- mucolipidosis IV
ICD-10 online (WHO version 2019)

The Sialolipidose , as mucolipidosis IV called, is an extremely rare autosomal - recessive inherited neurodegenerative lysosomal storage disease .

Incidence

Autosomal recessive inheritance

Sialolipidosis is an extremely rare disease with an incidence less than 1: 1 million. In the population of Ashkenazi Jews , the incidence is significantly higher at around 1 in 40,000. The heterozygote frequency there is accordingly 1: 100.

Symptoms

The affected patients suffer from psychomotor retardation and anomalies of the eyes , such as corneal opacity , retinal degeneration or squinting (strabismus). These symptoms can be observed from the first year of life, but sometimes also later. The progression of sialolipidosis is rather slow in most cases. Phospholipids , gangliosides and glycosaminoglycans are stored in the lysosomal inclusion bodies of the cells of the patient .

Genetics and Pathogenesis

Sialolipidosis is based on an autosomal recessive inheritance . Mutations in MCOLN1 - gene , located on 19 chromosome gene locus p13.3-P13.2 is ultimately the cause of the disease. MCOLN1 codes for the gene product TRPML1 (mucolipin-1); a 65  kDa heavy membrane protein with six transmembrane domains. It is from the family of the TRP channels ( transient receptor potential ). TRPML1 is an endo-lysosomal channel for iron ions.

From MCOLN1 gene so far about 20 different mutations have been described, two of which cause 95% of all mutations found in Ashkenazi Jews.

The cause of the accumulation of phospholipids, gangliosides and glycosaminoglycans in the lysosome is likely to be a disruption of the endocytosis of components of the cell membrane in the lysosomes.

diagnosis

The diagnosis of sialolipidosis is usually made by detecting the mutation in the MCOLN1 gene. The electron microscopic examination of the cell organelles, which are typically affected in mucolipidosis, is simpler . The prenatal diagnosis is possible by examining the amniotic cells or the chorion with an electron microscope .

A DNA analysis ('genetic test') of the parents is also possible prenatal.

therapy

A cure is so far excluded. The treatment is symptomatic.

Initial description

In 1974, ER Berman and colleagues first described sialolipidosis in sick Ashkenazi Jews as a new variant of mucolipidosis.

further reading

  • B. Venugopal et al.: Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IV. In: Am J Hum Genet 81, 2007, pp. 1070-1083. doi : 10.1086 / 521954 PMID 17924347 .
  • E. Goldin et al.: Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV. In: Hum Mutat 24, 2004, pp. 460-465. PMID 15523648
  • SM Pradhan et al: Electronegative electroretinogram in mucolipidosis IV. In: Arch Ophthal 120, 2002, pp. 45-50. PMID 11786056
  • R. Schiffmann et al.: Constitutive achlorhydria in mucolipidosis type IV. In: PNAS 95, 1998, pp. 1207-1212. PMID 9448310
  • KP Frei among others: Mucolipidosis type IV: characteristic MRI findings. In: Neurology 51, 1998, pp. 565-569. PMID 9710036
  • R. Bargal and G. Bach et al .: Mucolipidosis type IV: abnormal transport of lipids to lysosomes. In: J Inherit Metab Dis 20, 1997, pp. 625-632. PMID 9323557
  • RD Folkerth et al: Mucolipidosis IV: morphology and histochemistry of an autopsy case. In: J Neuropath Exp Neurol 54, 1995, pp 154-164. PMID 7876885
  • D. Chitayat et al .: Mucolipidosis type IV: clinical manifestations and natural history. In: Am J Med Genet 41, 1991, pp. 313-318. PMID 1789285
  • BD Lake et al: A mild variant of mucolipidosis type 4 (ML4). In: Birth Defects Orig Art Ser 18, 1982, pp. 391-404. PMID 7171767
  • Y. Ben-Yoseph et al: Catalytically defective ganglioside neuraminidase in mucolipidosis IV. In: Clin Genet 21, 1982, pp. 374-381. PMID 6813002
  • BF Crandall et al.: Mucolipidosis IV. In: Am J Med Genet 12, 1982, pp. 301-308. PMID 7114093
  • L. Caimi et al .: Mucolipidosis IV, a sialolipidosis due to ganglioside sialidase deficiency. In: J Inherit Metab Dis 5, 1982, pp. 218-224. PMID 6820444
  • F. Goutieres et al.: Mucolipidosis IV. In: Neuropaediatrie 10, 1979, pp. 321-330.
  • S. Merin et al .: Mucolipidosis IV: ocular, systemic, and ultrastructural findings. In: Invest Ophthal 14, 1975, pp. 437-448. PMID 166049
  • FW Newell et al .: A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration. In: Am J Ophthal 80, 1975, pp 440-449. PMID 169696

Web links

Individual evidence

  1. ↑ H. Denk, HP Dienes and J. Düllmann: Pathology of the liver and biliary tract. Verlag Springer, ISBN 3-540-65501-8 , p. 255.
  2. ↑ a b c d e f sialolipidosis. In: Orphanet (Rare Disease Database).
  3. ^ A. Raas-Rothschild et al.: Mucolipidosis type IV: the origin of the disease in the Ashkenazi Jewish population. In: Europ J Hum Genet 7, 1999, pp. 496-498. PMID 10352940
  4. ^ KG Riedel et al.: Ocular abnormalities in mucolipidosis IV. In: Am J Ophthal 99, 1985, pp. 125-136. PMID 3918453
  5. ↑ SA Slaugenhaupt et al .: Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes. In: Am J Hum Genet 65, 1999, pp. 773-778. PMID 10441585
  6. ↑ R. Bargal et al.: Identification of the gene causing mucolipidosis type IV. In: Nature Genet 26, 2000, pp. 118-121. PMID 10973263
  7. ↑ M. Sun et al .: Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. In: Hum Molec Genet 9, 2000, pp. 2471-2478. PMID 11030752
  8. ↑ X. Dong et al: The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endo-lysosomal Iron Release Channel. In: Nature 455, 2008, p. 992. doi : 10.1038 / nature07311 PMID 18794901
  9. ↑ N. Amir et al .: Mucolipidosis type IV: clinical spectrum and natural history. In: Pediatrics 79, 1987, pp. 953-959. PMID 2438637
  10. ↑ G. Kohn et al: Prenatal diagnosis of mucolipidosis IV by electron microscopy. In: J Pediat 90, 1977, pp. 62-66. PMID 830895
  11. ↑ A. Ornoy et al.: Early prenatal diagnosis of mucolipidosis IV. (Letter) In: Am J Med Genet 27, 1987, pp. 983-985. PMID 3425607
  12. ↑ ER Berman et al.: Congenital corneal clouding with abnormal systemic storage bodies: a new variant of mucolipidosis. In: J Pediat 84, 1974, pp. 519-526. PMID 4365943