Fabry disease
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Fabry disease was first described in 1898 independently by Anderson [1] in England and Fabry [2] in Germany. The latter name has become its designation [3], possibly because Fabry continued to publish information about his patient over a 32-year period [4]. Anderson and Fabry each recognized the systemic nature of the disease but, as dermatologists, their focus was on the cutaneous angiokeratomas by which the patient is so readily recognized. The disease is also known as angiokeratoma corporis diffusum universale [5–7]. It was first noted to be X-linked by Opitz and colleagues in 1965 [7]. The disorder was appropriately classified as a glycosphingolipidosis following the isolation and characterization by Sweeley and Klionsky [8] of the Fabry lipid as galactosylgalactosylglucosylceramide (Figure 87.1). The molecular defect was demonstrated by Brady and colleagues [9] as an inability to cleave the terminal galactose from this ceramide trihexoside; thus, the defective activity is ceramide trihexosidase (Figure 87.1). The defective enzyme was shown by Kint [10] by means of an artificial substrate to be an α-galactosidase. It is referred to as α-galactosidase A to distinguish it from the α-N-acetylgalactosaminidase which is deficient in Schindler disease and is also an α-galactosidase (B). The gene is on the X chromosome at Xq22.1 [11] and the disease is expressed as an X-linked dominant. The gene has been cloned and its sequence determined [12–13]. A large number and variety of mutations have been defined. Among 34 different mutations 76 percent were missense, 16 percent nonsense and the rest splice site and frameshift mutations [14].
Low α-N-acetylgalactosaminidase plasma concentration correlates with the presence and severity of the bipolar affective disorder
Published in The World Journal of Biological Psychiatry, 2023
This study had limitations. A limited number of patients and healthy controls were included. New studies with more participants are needed to generalise the results. No studies on α-N-acetylgalactosaminidase have ever been conducted in BAD. And previous studies in different diseases related to α-N-acetylgalactosaminidase were molecular and genetic studies showing enzyme activity (Michalski and Klein 1999). In addition, some pathological (Desnick and Wang 1990) and immunocytochemical (Sakuraba et al. 2004) studies were available. Similar studies can be conducted to increase the significance and support the key findings obtained by our study. In our study, the patients were under drug treatment and there was no significant difference between the drugs they used and their α-NAGAL levels. This study included a small number of patients, and it may be possible for drugs to alter α-NAGAL activity and levels in studies with larger participants. Or, new studies with patients who do not use drugs may give clearer results. How α-NAGAL deficiency leads to BAD still remains unanswered, which we believe researchers should investigate which glycoprotein has pathology in its catalysis. Although our results, from where we stand, support the neurodevelopmental hypothesis, it is crucial to conduct prenatal studies to further investigate and prove this suggestion.
Could low α-N-acetylgalactosaminidase plasma concentration cause schizophrenia?
Published in The World Journal of Biological Psychiatry, 2023
α-N-acetylgalactosaminidase (α-NAGAL) (E.C. 3.2.1.49) is a lysosomal enzyme, a hydrolase that catalyses the removal of terminal α-linked N-acetylgalactosamine (α-GalNAc) and, to a lesser extent, galactose monosaccharides. The human gene encoding the α-N-acetylgalactosaminidase enzyme is NAGA. Mutations in this gene and resulting decreases in enzyme activity have been shown to cause Schindler's disease, which shows some neurological and psychiatric symptoms (Wang et al. 1990).
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