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

Abstract

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.

Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements

“…Although the screening strategy included in the nomination of KD to the RUSP had been recommended in previous publications [12,13], discussion among the authors identified several reasons for the lack of adoption by all NBS programs. One is the difficulty of state programs to adjust existing screening algorithms due to the concern, only supported by anecdotal reports [24], of possibly missing patients with IKD or even an AKD case following a change that focuses on IKD and LIKD as the primary targets of screening. Several programs rely on their advisory committees to determine screening algorithms, some even to set cutoffs.…”

“Atypical” Krabbe disease in two siblings harboring biallelic GALC mutations including a deep intronic variant

“…Galactosylsphingosine, also known as psychosine, is a wellknown biomarker for early-onset form and its measurement in dried blood spots is improving the newborn screening programs for KD; nevertheless, lower or normal values of psychosine may be present in late-onset phenotype [10,11]. In our patients, we determined the levels of HexSph (galactosylsphingosine + glucosylsphingosine) by liquid chromatography coupled with tandem mass spectrometry, a validate method for simultaneous quantification of several lysosphingolipids [12].…”

Globoid Cell Leukodystrophy (Krabbe Disease): An Update

“…11 A patient who developed KD in late infancy had a pathogenic genotype, showed reduced enzyme activity but surprisingly low psychosine levels, suggesting that measuring psychosine levels should be combined with other measurements, such as enzyme levels, as well as genotyping and correlation with the patient's clinical presentations. 40 Therefore, magnetic resonance (MR) images showing abnormal signals, as well as the presence of globoid cells must be done before final diagnosis of the disease. 41 For instance, MR imaging diagnosed A 32-year-old woman with headache as adult onset KB with two pathogenic variants in GALC.…”