Newborn Screening for Krabbe Disease—Illinois Experience: Role of Psychosine in Diagnosis of the Disease

Abstract

Population-based newborn screening for Krabbe disease was initiated by measurement of galactocerebrosidase (GALC) activity in the state of Illinois in December 2017. Due to the poor specificity of GALC for the diagnosis of Krabbe disease, second-tier testing services were provided to reduce the false positive rates for disease monitoring. Using ultra-pressure liquid chromatography coupled to mass spectrometry assay, a total of 497,147 newborns were screened. In total, 288 infants’ specimens (0.06%) having reduced GALC activity were sent out for second-tier testing to a reference laboratory. All newborns’ reduced GALC specimens were tested for psychosine levels, the presence of a 30-kb deletion and GALC sequencing. The results showed that two infants had elevated psychosine levels (10 and 35 nM) and were referred immediately for evaluation and treatment for Infantile Krabbe disease, and six infants had intermediate PSY levels (≥2 to 5 nM) and are under observation as suspected candidates for late-onset Krabbe disease. In addition, 178 infants had pseudodeficiency alleles, all having psychosine levels < 2.0 nM. Our data show that a high percentage of reduced GALC activity (62%) was due to the presence of pseudodeficiency alleles in the GALC gene. In conclusion, incorporation of psychosine measurements can identify infants with infantile Krabbe disease and probable late-onset Krabbe infants. Furthermore, Krabbe disease screening can be achieved at public health laboratories, and infants with infantile Krabbe disease can be diagnosed in timely manner for better outcome.

Advances in the Diagnosis and Treatment of Krabbe Disease

“…In individuals with a psychosine concentration over 2 nmol/L, mutation analysis and neuro-diagnostic studies may be indicated, but it is not a first priority [17,18].…”

“…Values under 2 nmol/L indicate that the individual probably will not develop Krabbe disease. In individuals with a psychosine concentration over 2 nmol/L, mutation analysis and neurodiagnostic studies may be indicated, but it is not a first priority [17,18].…”

“…In fact, in 1980, Svennerholm et al [16] called Krabbe disease a psychosine lipidosis. More about the significance of elevated psychosine as a second-tier test in the diagnosis of Krabbe disease has recently been published [17,18].…”

The Editor’s Choice for Issue 2, Volume 7

“…Dear readers: I am proud to say that we are continuing to publish many important papers on newborn screening in IJNS , and the papers published in this issue clearly support my statement. Please allow me to highlight two papers published by Basheeruddin et al [ 1 ] and Corre et al [ 2 ] on newborn screening for Krabbe disease (KD) in this issue. Much more information is needed regarding this rare disease to inform discussion among researchers, clinicians and public advocates about whether it should be included as a part of the federal RUSP in the United States.…”

“…The first paper by Basheeruddin et al [ 1 ] presents three years of Krabbe NBS experience in Illinois and discusses the results of analyzing psychosine as a second-tier test. The Illinois state NBS program performs GALC enzyme test as a first-tier assay and adds genetic tests with analyses of psychosine levels when newborns have low GALC enzyme levels.…”