A view on sphingolipids and disease

Kolter, Thomas

doi:10.1016/j.chemphyslip.2011.04.013

Cited by 77 publications

(56 citation statements)

References 185 publications

(173 reference statements)

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“…Decrease of enzyme activity to the calculated threshold value does not influence the turnover rate of the substrate (as above this threshold, there is no (linear) relation between enzyme activity and turnover) and pathological storage occurs only below this level. With the exception of acid ceramidase, a decrease of enzyme activity to values of 20 % of normal cells, a typical range for heterozygote carriers of inherited diseases, has no impact on the turnover rate (Kolter 2011). Our findings corroborate these findings, as we found no deposition of Gb-3 in the lysosomes of the cells of our patients with the p. Ala143Thr mutation.…”

Section: Discussionsupporting

confidence: 90%

“…In the sphingolipidosis, the ratio of substrate influx into the lysosome and the capacity of the degrading system determines the storage and as such the course and severity of the disease. This is treated in quantitative terms by the so-called threshold theory (Kolter 2011). Only the decrease of enzyme activity below the critical threshold value causes storage of the corresponding lipid substrate.…”

Section: Discussionmentioning

confidence: 99%

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Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

et al. 2012

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Fabry disease is an X-linked inborn error of glycosphingolipid metabolism caused by quantitative or qualitative defects in the lysosomal enzyme alfa-Galactosidase A (aGAL A), ultimately resulting in vital organ dysfunction. Mainly the kidneys, the heart, and the central nervous system are involved. While the classical phenotype of Fabry disease is readily recognizable, screening studies have identified clinical variants. Here, we report the phenotype associated with the GLA p.Ala143Thr (c.427G>A) mutation in 12 patients aged 42-83 years. None of the patients had classical Fabry signs or symptoms as angiokeratoma, hypohidrosis, acroparesthesia, or cornea verticillata. Possible Fabry manifestations were renal failure (5/12), stroke (7/12), and left ventricular hypertrophy (5/12), but these were not necessarily attributable to the p.Ala143Thr mutation, as a cardiac biopsy in one female and left ventricular hypertrophy and kidney biopsies in two males with renal failure and microalbuminuria lacked Gb-3 deposits. The literature data on this mutation as well as data collected in the Fabry Outcome Survey (FOS) database confirm these findings. The association of renal failure, stroke, and left ventricular hypertrophy with this mutation could be the result of selection bias, as most patients were detected in screening studies.We conclude that care should be taken with attribution of vital organ dysfunction to GLA sequence alterations. In case of the p.Ala143Thr mutation, and possibly also other mutations associated with an attenuated phenotype, diagnostic tools such as biopsy and imaging should critically evaluate the relation of end-organ failure with Fabry disease, as this has important consequences for enzyme replacement therapy.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

et al. 2012

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“…They are highly diverse in eukaryotes and play important roles in the survival and development of cells. Moreover, alterations in sphingolipid metabolism are the cause of several human diseases (35). Sphingolipids have also been shown to be involved in development in fungi (36), as an example of lower eukaryotic organisms.…”

Section: Discussionmentioning

confidence: 99%

Neutral and Phospholipids of the Myxococcus xanthus Lipodome during Fruiting Body Formation and Germination

Ahrendt

Wolff

Bode

2015

Appl Environ Microbiol

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“…Cer, ceramide; dHCer, dihydroceramide; SM, sphingomyelin; HexCer, hexosylceramide; LacCer, lactosylceramide. diabetes, cardiovascular disease, and various cancer diseases as well as central nervous system diseases [7][8][9][10]. To expand our knowledge of this lipid family, development of sensitive, robust and structural-specific methods enabling fast determination of as many sphingolipid species as possible are required.…”

Section: Introductionmentioning

confidence: 99%

Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: Method development and application in hepatocellular carcinoma

Zhao

et al. 2013

Journal of Chromatography A

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A view on sphingolipids and disease

Cited by 77 publications

References 185 publications

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

Neutral and Phospholipids of the Myxococcus xanthus Lipodome during Fruiting Body Formation and Germination

Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: Method development and application in hepatocellular carcinoma

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