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

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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Newborn Screening for Krabbe Disease: the New York State Model

Pediatric Neurology ◽

10.1016/j.pediatrneurol.2009.01.001 ◽

2009 ◽

Vol 40 (4) ◽

pp. 253-255 ◽

Cited By ~ 2

Author(s):

Robert D. Steiner

Keyword(s):

New York ◽

Newborn Screening ◽

New York State ◽

Krabbe Disease ◽

State Model ◽

York State

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Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State

Genetics in Medicine ◽

10.1038/gim.2016.35 ◽

2016 ◽

Vol 18 (12) ◽

pp. 1235-1243 ◽

Cited By ~ 48

Author(s):

Melissa P. Wasserstein ◽

◽

Mary Andriola ◽

Georgianne Arnold ◽

Alan Aron ◽

...

Keyword(s):

New York ◽

Newborn Screening ◽

Clinical Outcomes ◽

New York State ◽

Krabbe Disease ◽

York State

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Diagnosis of Huntington Disease

Clinical Chemistry ◽

10.1373/49.10.1726 ◽

2003 ◽

Vol 49 (10) ◽

pp. 1726-1732 ◽

Cited By ~ 68

Author(s):

Russell L Margolis ◽

Christopher A Ross

Keyword(s):

Huntington Disease ◽

Clinical Presentation ◽

Neurodegenerative Disorder ◽

Diagnostic Testing ◽

Disease Onset ◽

Test Results ◽

Genetic Test Results ◽

Essential Components ◽

Trinucleotide Expansion ◽

Expansion Mutation

Abstract Background: Huntington disease (HD) is a rare, progressive, and fatal autosomal dominant neurodegenerative disorder, typically of adult onset. Methods: We reviewed the literature concerning the molecular diagnosis of HD. Results: The discovery of the genetic etiology of HD, a trinucleotide expansion mutation on chromosome 4p, has led to the development of increasingly reliable and valid diagnostic tests that can be applied to symptomatic patients, individuals at risk for HD but currently asymptomatic, fetuses, and embryos. However, the unstable nature of the HD mutation, the lack of effective treatments for HD, the mid-adulthood age of disease onset, and the existence of disorders with the same clinical presentation but different etiology all complicates diagnostic testing. Conclusion: Conscientious laboratory work, knowledgeable interpretation of genetic test results, and the availability of pre- and posttest counseling are essential components of HD diagnosis.

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Newborn Screening for Krabbe Disease: the New York State Model

Pediatric Neurology ◽

10.1016/j.pediatrneurol.2008.11.010 ◽

2009 ◽

Vol 40 (4) ◽

pp. 245-252 ◽

Cited By ~ 136

Author(s):

Patricia K. Duffner ◽

Michele Caggana ◽

Joseph J. Orsini ◽

David A. Wenger ◽

Marc C. Patterson ◽

...

Keyword(s):

New York ◽

Newborn Screening ◽

New York State ◽

Krabbe Disease ◽

State Model ◽

York State

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Effect of Statewide Lockdown in Response to COVID-19 Pandemic on Physical Activity Levels of Hemodialysis Patients

Blood Purification ◽

10.1159/000514935 ◽

2021 ◽

pp. 1-8

Author(s):

Maggie Han ◽

Priscila Preciado ◽

Ohnmar Thwin ◽

Xia Tao ◽

Leticia M. Tapia-Silva ◽

...

Keyword(s):

Physical Activity ◽

New York ◽

New York City ◽

New York State ◽

Hemodialysis Patients ◽

Activity Levels ◽

Physical Activity Levels ◽

National Emergency ◽

The Impact

Background/Objectives: On March 22, 2020, a statewide stay-at-home order for nonessential tasks was implemented in New York State. We aimed to determine the impact of the lockdown on physical activity levels (PAL) in hemodialysis patients. Methods: Starting in May 2018, we are conducting an observational study with a 1-year follow-up on PAL in patients from 4 hemodialysis clinics in New York City. Patients active in the study as of March 22, 2020, were included. PAL was defined by steps taken per day measured by a wrist-based monitoring device (Fitbit Charge 2). Average steps/day were calculated for January 1 to February 13, 2020, and then weekly from February 14 to June 30. Results: 42 patients were included. Their mean age was 55 years, 79% were males, and 69% were African Americans. Between January 1 and February 13, 2020, patients took on average 5,963 (95% CI 4,909–7,017) steps/day. In the week prior to the mandated lockdown, when a national emergency was declared, and in the week of the shutdown, the average number of daily steps had decreased by 868 steps/day (95% CI 213–1,722) and 1,222 steps/day (95% CI 668–2300), respectively. Six patients were diagnosed with COVID-19 during the study period. Five of them exhibited significantly higher PAL in the 2 weeks prior to showing COVID-19 symptoms compared to COVID-19 negative patients. Conclusion: Lockdown measures were associated with a significant decrease in PAL in hemodialysis patients. Patients who contracted COVID-19 had higher PAL during the incubation period. Methods to increase PAL while allowing for social distancing should be explored and implemented.

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Long-Term Neurodevelopmental Outcomes of Hematopoietic Stem Cell Transplantation for Late-Infantile Krabbe Disease

Blood ◽

10.1182/blood.2020005477 ◽

2020 ◽

Author(s):

Isabel C Yoon ◽

Nicholas A Bascou ◽

Michele D Poe ◽

Paul Szabolcs ◽

Maria L Escolar

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Symptom Onset ◽

Disease Onset ◽

Krabbe Disease ◽

Hematopoietic Stem ◽

Prospective Longitudinal

Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in galactocerebrosidase. The only effective treatment is hematopoietic stem cell transplantation (HSCT). Approximately 85% of Krabbe cases are the infantile subtypes, among which ~20% are late-infantile. Prior studies demonstrated that HSCT is effective for early-infantile patients (0 - 6 months of age) transplanted while asymptomatic, compared to those transplanted while symptomatic. However, no studies evaluated the efficacy of HSCT for late-infantile patients (6 - 36 months). In this prospective, longitudinal study, patients were evaluated at a single site following a standardized protocol. Survival analysis was performed using the Kaplan-Meier method. Differences between groups were estimated using Mixed Regression models to account for within person repeated measures. Nineteen late-infantile patients underwent HSCT (1997 - 2020). Compared to untreated patients, transplanted patients had a longer survival probability and improved cognitive and language function. Gross and fine motor development were most affected with variable results. Asymptomatic patients benefitted the most from transplantation with normal to near-normal development in all domains and some gross motor delays. Among symptomatic patients, those with disease onset > 12 months of age had better cognitive outcomes than untreated patients. Those with disease onset £ 12 months were comparable to untreated patients. We found that HSCT prolongs the lifespan and improves the functional abilities of late-infantile Krabbe patients, particularly for those transplanted before symptom onset. In addition, our findings support prior literature that reclassifies late-infantile Krabbe disease to be symptom onset 12 to 36 months of age.

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