Psychosine, a marker of Krabbe phenotype and treatment effect

Escolar, Maria L.; Kiely, Bridget; Shawgo, Emily P.R.; Hong, Xinying; Gelb, Michael H.; Orsini, Joseph J.; Matern, Dietrich; Poe, Michele D.

doi:10.1016/j.ymgme.2017.05.015

Cited by 57 publications

(71 citation statements)

References 14 publications

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“…In all infantile KD cases (n = 8), we observed a moderate LysoHexCer increase, which corroborates with results obtained by others (Kuchař et al 2013 in DBS;Polo et al 2017, Zhao et al 2017, Escolar et al 2017. Thus, the LSL-based screening of infantile KD is possible and less sample-consuming than galactocerebrosidase activity determination in leukocytes.…”

Section: Lysosphingolipidssupporting

confidence: 91%

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Piraud

Pettazzoni

Lavoie

et al. 2018

J of Inher Metab Disea

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Tandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of lysosomal storage disorders (LSDs) and how MS/MS has changed the diagnostic rationale in recent years. This fine technology brings more sensitive, specific, and reliable methods than the previous biochemical ones for the analysis of urinary glycosaminoglycans, oligosaccharides, and sialic acid. In sphingolipidoses, the quantification of urinary sphingolipids (globotriaosylceramide, sulfatides) is possible. The measurement of new plasmatic biomarkers such as oxysterols, bile acids, and lysosphingolipids allows the screening of many sphingolipidoses and related disorders (Niemann-Pick type C), replacing tedious biochemical techniques. Applied to amniotic fluid, a more reliable prenatal diagnosis or screening of LSDs is now available for fetuses presenting with antenatal manifestations. Applied to enzyme measurements, it allows high throughput assays for the screening of large populations, even newborn screening. The advent of this new method can modify the diagnostic rationale behind LSDs.

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Section: Lysosphingolipidssupporting

confidence: 91%

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Piraud

Pettazzoni

Lavoie

et al. 2018

J of Inher Metab Disea

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“…For diagnosis and treatment of Krabbe disease, psychosine (galactosylsphingosine) analysis is applied as a marker in a blood test [116]. Hematopoietic stem cell transplantation serves as a therapeutic approach of Krabbe disease.…”

Section: Krabbe Diseasementioning

confidence: 99%

Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease

Breiden

Sandhoff

2020

IJMS

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Gangliosidoses are caused by monogenic defects of a specific hydrolase or an ancillary sphingolipid activator protein essential for a specific step in the catabolism of gangliosides. Such defects in lysosomal function cause a primary accumulation of multiple undegradable gangliosides and glycosphingolipids. In reality, however, predominantly small gangliosides also accumulate in many lysosomal diseases as secondary storage material without any known defect in their catabolic pathway. In recent reconstitution experiments, we identified primary storage materials like sphingomyelin, cholesterol, lysosphingolipids, and chondroitin sulfate as strong inhibitors of sphingolipid activator proteins (like GM2 activator protein, saposin A and B), essential for the catabolism of many gangliosides and glycosphingolipids, as well as inhibitors of specific catabolic steps in lysosomal ganglioside catabolism and cholesterol turnover. In particular, they trigger a secondary accumulation of ganglioside GM2, glucosylceramide and cholesterol in Niemann-Pick disease type A and B, and of GM2 and glucosylceramide in Niemann-Pick disease type C. Chondroitin sulfate effectively inhibits GM2 catabolism in mucopolysaccharidoses like Hurler, Hunter, Sanfilippo, and Sly syndrome and causes a secondary neuronal ganglioside GM2 accumulation, triggering neurodegeneration. Secondary ganglioside and lipid accumulation is furthermore known in many more lysosomal storage diseases, so far without known molecular basis.

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“…Psychosine may then be measured during follow-up of the abnormal newborn screening result. Psychosine has also been evaluated as a biomarker to predict the severity of Krabbe disease [1,3,[7][8][9]. For patients tested at the Mayo Clinic, those with psychosine of greater than ~10 nM in DBS are considered at high risk to develop early-onset Krabbe disease (symptoms during the first year of life), whereas patients who develop later-onset Krabbe disease typically have psychosine values in the 2-10 nM range.…”

Section: Introductionmentioning

confidence: 99%

Achieving Congruence among Reference Laboratories for Absolute Abundance Measurement of Analytes for Rare Diseases: Psychosine for Diagnosis and Prognosis of Krabbe Disease

Herbst

Turgeon

Biski

et al. 2020

IJNS

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Measurement of the absolute concentration of the biomarker psychosine in dried blood spots (DBS) is useful for diagnosis and prognosis of Krabbe disease and to support newborn screening of this leukodystrophy. As for assays for more common diseases, it is important to achieve congruence when multiple clinical laboratories provide testing. Four clinical laboratories, one research laboratory, and a commercial vendor collaborated with the goal to achieve congruence in quantitative psychosine measurement in DBS. A set of DBS calibrators was prepared by a single vendor and used in each reference laboratory to make a standard curve of measured psychosine in DBS versus the stated calibrator psychosine level. Congruence between the participating five laboratories was achieved using the psychosine DBS calibrators. This allowed application of disease-specific reference ranges obtained by the reference laboratory with the most extensive data by the other reference laboratories. Congruence between multiple reference laboratories in the measurement of the absolute concentration of biomarkers in DBS (and by extension other samples) is possible by the use of a common set of DBS calibrators.

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Psychosine, a marker of Krabbe phenotype and treatment effect

Cited by 57 publications

References 14 publications

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease

Achieving Congruence among Reference Laboratories for Absolute Abundance Measurement of Analytes for Rare Diseases: Psychosine for Diagnosis and Prognosis of Krabbe Disease

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