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

Herbst, Zackary M.; Turgeon, Coleman T.; Biski, Chad K.; Khaledi, Hamid; Shoemaker, Nancy B; DeArmond, Patrick D.; Smith, Sara N.; Orsini, Joseph J.; Matern, Dietrich; Gelb, Michael H.

doi:10.3390/ijns6020029

Cited by 9 publications

(10 citation statements)

References 10 publications

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“…Psy levels provide invaluable information as part of NBS for KD and their measurement as a second-tier test has improved the specificity of NBS for KD. While the case presented here has led to the revision of Psy cutoffs in DBS and an attempt to standardize results between laboratories providing Psy testing [29], it is unlikely that 100% sensitivity can be achieved without considerable negative impact on specificity [8,30]. Finally, it cannot be overemphasized that Psy levels must be reviewed as just one of several important factors in determining the diagnosis and follow-up plan of a patient who screens positive.…”

Section: Discussionmentioning

confidence: 92%

Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

Corre

Matern

Pellegrino

et al. 2021

IJNS

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Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease. This report describes a patient who was screened positive for KD in New York State, had a likely pathogenic genotype, and showed markedly reduced enzyme activity but surprisingly low psychosine levels. The patient ultimately developed KD in late infancy, an outcome not clearly predicted by existing NBS algorithms. It remains critical that psychosine levels be evaluated alongside genotype, enzyme activity levels, and the patient’s evolving clinical presentation, ideally in consultation with experts in KD, in order to guide diagnosis and plans for monitoring.

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Section: Discussionmentioning

confidence: 92%

Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

Corre

Matern

Pellegrino

et al. 2021

IJNS

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“…Before the development of the chromatographic separation method, we were aware of the existence of psychosine, a biomarker increased in Krabbe disease [ 32 ] which might interfere with the quantitation of lyso-Gb 1 considering that it is a molecule with physical and chemical properties similar to lyso-Gb 1 [ 33 ]. Therefore, in order to properly characterize the compound identified and better understand the physiopathology of Gaucher disease, a separation of psychosine and lyso-Gb 1 is preferred.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach

Menkovic

Boutin

Alayoubi

et al. 2020

IJMS

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Gaucher disease (GD) is a rare autosomal recessive multisystemic lysosomal storage disorder presenting a marked phenotypic and genotypic variability. GD is caused by a deficiency in the glucocerebrosidase enzyme. The diagnosis of GD remains challenging because of the large clinical spectrum associated with the disease. Moreover, GD biomarkers are often not sensitive enough and can be subject to polymorphic variations. The main objective of this study was to perform a metabolomic study using an ultra-performance liquid chromatography system coupled to a time-of-flight mass spectrometer to identify novel GD biomarkers. Following the analysis of plasma samples from patients with GD, and age- and gender-matched control samples, supervised statistical analyses were used to find the best molecules to differentiate the two groups. Targeted biomarkers were structurally elucidated using accurate mass measurements and tandem mass spectrometry. This metabolomic study was successful in highlighting seven biomarkers associated with GD. Fragmentation tests revealed that these latter biomarkers were lyso-Gb1 (glucosylsphingosine) and four related analogs (with the following modifications on the sphingosine moiety: -C2H4, -H2, -H2+O, and +H2O), sphingosylphosphorylcholine, and N-palmitoyl-O-phosphocholineserine. Based on the plasma biomarker distribution, we suggest the evaluation of this GD biomarker profile, which might facilitate early diagnosis, monitoring, and follow-up of patients.

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“…Newborn screenings are available for Krabbe disease with measurement of GALC enzymatic activity in DBS and measurement of psychosine in DBS as second-tier test may help to differentiate infantile from late-onset KD variants, as well as from GALC variant and pseudodeficiency carriers [ 165 ]. Psychosine concentrations have also been evaluated as biomarker to predict the severity of disease considering patients with psychosine greater concentrations at high risk to develop early-onset KD [ 166 ].…”

Section: Demyelinating Neuropathiesmentioning

confidence: 99%

Inherited Neuromuscular Disorders: Which Role for Serum Biomarkers?

et al. 2021

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Inherited neuromuscular disorders (INMD) are a heterogeneous group of rare diseases that involve muscles, motor neurons, peripheral nerves or the neuromuscular junction. Several different lab abnormalities have been linked to INMD: sometimes they are typical of the disorder, but they usually appear to be less specific. Sometimes serum biomarkers can point out abnormalities in presymtomatic or otherwise asymptomatic patients (e.g., carriers). More often a biomarker of INMD is evaluated by multiple clinicians other than expert in NMD before the diagnosis, because of the multisystemic involvement in INMD. The authors performed a literature search on biomarkers in inherited neuromuscular disorders to provide a practical approach to the diagnosis and the correct management of INMD. A considerable number of biomarkers have been reported that support the diagnosis of INMD, but the role of an expert clinician is crucial. Hence, the complete knowledge of such abnormalities can accelerate the diagnostic workup supporting the referral to specialists in neuromuscular disorders.

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

Cited by 9 publications

References 10 publications

Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach

Inherited Neuromuscular Disorders: Which Role for Serum Biomarkers?

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