Health Conditions Related to Genetic Changes
Alpha-N-acetylgalactosaminidase deficiency
Variants (also called mutations) in the NAGA gene on chromosome 22 have been identified in people with alpha-N-acetylgalactosaminidase deficiency. This condition affects the nervous system, and it is sometimes called Schindler disease. The three types of alpha-N-acetylgalactosaminidase deficiency differ in the severity of their signs and symptoms and the age at which they first appear. Most of these variants result in the substitution of one protein building block (amino acid) for another. These changes are believed to alter the shape of the alpha-N-acetylgalactosaminidase enzyme. The change in the protein’s shape can interfere with its ability to break down glycoproteins and glycolipids. As these substances accumulate in the lysosomes, they may cause cells to malfunction and eventually die. Cell damage in the various tissues and organs of the body leads to neurological problems and the other signs and symptoms of this disorder. It is unclear how NAGA gene variants lead to the wide range of signs and symptoms seen in affected individuals.
More About This Health ConditionOther Names for This Gene
- alpha-galactosidase B
- alpha-N-acetylgalactosaminidase precursor
- D22S674
- GALB
- N-acetyl-alpha-D-galactosaminidase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Clark NE, Garman SC. The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases. J Mol Biol. 2009 Oct 23;393(2):435-47. doi: 10.1016/j.jmb.2009.08.021. Epub 2009 Aug 14. Citation on PubMed or Free article on PubMed Central
- Desnick RJ, Wang AM. Schindler disease: an inherited neuroaxonal dystrophy due to alpha-N-acetylgalactosaminidase deficiency. J Inherit Metab Dis. 1990;13(4):549-59. doi: 10.1007/BF01799512. Citation on PubMed
- Kanekura T, Sakuraba H, Matsuzawa F, Aikawa S, Doi H, Hirabayashi Y, Yoshii N, Fukushige T, Kanzaki T. Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes. J Dermatol Sci. 2005 Jan;37(1):15-20. doi: 10.1016/j.jdermsci.2004.09.005. Epub 2004 Dec 8. Citation on PubMed
- Keulemans JL, Reuser AJ, Kroos MA, Willemsen R, Hermans MM, van den Ouweland AM, de Jong JG, Wevers RA, Renier WO, Schindler D, Coll MJ, Chabas A, Sakuraba H, Suzuki Y, van Diggelen OP. Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. J Med Genet. 1996 Jun;33(6):458-64. doi: 10.1136/jmg.33.6.458. Citation on PubMed or Free article on PubMed Central
- Michalski JC, Klein A. Glycoprotein lysosomal storage disorders: alpha- and beta-mannosidosis, fucosidosis and alpha-N-acetylgalactosaminidase deficiency. Biochim Biophys Acta. 1999 Oct 8;1455(2-3):69-84. doi: 10.1016/s0925-4439(99)00077-0. Citation on PubMed
- Sakuraba H, Matsuzawa F, Aikawa SI, Doi H, Kotani M, Nakada H, Fukushige T, Kanzaki T. Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease). J Hum Genet. 2004;49(1):1-8. doi: 10.1007/s10038-003-0098-z. Epub 2003 Dec 19. Citation on PubMed
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