Connect with Us
Thomas Langan, MD
Professor of Neurology,
University at Buffalo
Clinical Center, HJKRI
Hunter James Kelly Research Institute -
To analyze data from the Krabbe newborn screening and World Wide Registry of Krabbe
patients to improve diagnosis and prognosis, and to provide outcome measures for clinical trials.
- Develop initiatives to maximize the success of the Newborn Screening program for Krabbe Disease
- Increase understanding of various types of Krabbe Disease, determine which biochemical, genetic, and neurodiagnostic tests predict phenotype
- Educate physicians about Krabbe Disease and Newborn Screening
- Develop clinical evaluation and treatment protocols for Krabbe Disease
What's going on in the Clinical Center?
The HJKRI Clinical Research Center has had four major goals since its inception in 2006:
- To improve outcomes of children identified with, or at risk for, Krabbe Disease through newborn screening in New York State
- To improve understanding of the natural history of Krabbe Disease
- To increase awareness of Krabbe Disease through education
- To provide clinical care
To achieve the first goal, the NYS Krabbe Consortium, a multidisciplinary group of child neurologists, geneticists, newborn screeners, neuroradiologists, transplanters and developmental pediatricians, was established in 2006 in response to the advent of newborn screening for Krabbe disease in NYS. In order to provide a consistent statewide approach to the process, the consortium identified risk groups of babies with positive newborn screens based on the amount of GALC activity found on confirmatory testing. Standardized baseline and long term neurodiagnostic protocols were established, in which the frequency and intensity of these evaluations was based on the child’s risk group. In addition a point system for referral for possible hematopoietic cell transplantation was established. The consortium also established a clinical/database
registry of children with positive newborns screens/confirmatory testing which was organized and located at the Clinical Center of the HJKRI. Additional goals of the registry include determining which neurodiagnostic tests, mass spectrometry, mutation analysis and/or GALC activity predict outcome and to modify mandated tests, where necessary, based on biannual review of testing results.
Members* of the Krabbe Consortium also participated in an HKJRI study in which at risk
children were monitored from birth to age two years using a phone-based interview
system in order to determine whether children with very low GALC activity but
no clinical evidence of Krabbe Disease were at risk for developmental problems;
to monitor children with low GALC activity to identify possible early signs of
Krabbe Disease between medical visits; and to assess the feasibility and
reliability of the phone based interview system. As a result of the work of the Krabbe
consortium, the NYS newborn screening program has been widely accepted as the model for
screening children with Krabbe and other lysosomal disorders.
goal of the Clinical Center is to improve understanding of the natural
history of Krabbe Disease including whether clinical, biochemical, genetic
and/or neurodiagnostic parameters might predict phenotype. To accomplish this goal, an international
registry of patients with Krabbe Disease was established in 2008 (the
World Wide Registry). Parent
questionnaires and medical records are accessed and reviewed with a focus on
clinical signs and symptoms, disease course, family history and results of
biochemical, genetic and neurodiagnostic studies. In order to increase the
number of patients with a known genotype, mutation analysis is performed on
saliva and newborn blood spots. Results are then compared with clinical course
to provide genotype/phenotype correlations. In addition, MRI discs from more than 70 patients are being reviewed in an
effort to correlate neuroradiologic findings with phenotype and disease course.
third goal of the Clinical Center is to increase awareness of Krabbe
Disease through education. To this end, the Clinical Director has been a
visiting professor throughout the US as well as at national and
international genetic, pediatric and neurology meetings discussing newborn screening
for Krabbe Disease and the clinical manifestations of this disorder. She has also
addressed state newborn screening advisory panels. The highly successful annual
workshop on Krabbe Disease has increased awareness of the condition as well as
fostered collaborations among investigators.
The fourth goal of the Clinical Center is to provide clinical care for children with Krabbe Disease as well as those with positive newborn screens for the disease. A clinic was established by the Clinical Director at the Women and Children’s Hospital of Buffalo. In the future, as new therapies come on line, we anticipate having an active translational research component to the Clinical Center.
*Additional members of the Krabbe Consortium include: Richard Erbe, MD; Jennifer Kwon, MD; Carl Crosley, MD; Ryan Miller;
Darius Adams, MD; David Kronn, MD; Alexandra Djukic, MD; Paul Levy, MD; Alan
Aron, MD; Melissa Wasserstein, MD; Mary Andriola, MD; Patricia Galvin-Parton,
Clinical Center Founder - Dr. Patricia Duffner, MD
Patricia K. Duffner established the Clinical Center of the HJKRI in 2006 and served as Clinical Director of the Institute until January 2012. She is currently a consultant to the Institute.
In 1997 she diagnosed four-month-old Hunter Kelly with Krabbe Disease, leading eventually to a shift in her research focus. She developed a lasting relationship with the Kelly family the Hunter's Hope Foundation, serving as chair of the Scientific Advisory Committee for many years.
In 2006, with the advent of newborn screening for Krabbe Disease in NYS, she focused her efforts on
maximizing the effectiveness of the NYS program and became Clinical Director of the Institute. She established the NYS Krabbe Consortium, the NYS Newborn Screening Clinical Database/Registry and the World Wide Registry for Krabbe Disease.
Clinical Center Collaborators:
|Randy L. Carter,
Professor of Biostatistics
MS Data Manager
MS, PhD Student
Professor of Pediatrics,
University of Chicago
Ahmed Abdelhalim, MD
Roswell Park Cancer Institute
Ronald Alberico, MD
Roswell Park Cancer Institute
Denise Kay, PhD
Albany, New York
Michele Caggana, PhD
Albany, New York
Joseph Orsini, PhD
Albany, New York
Steven Gill, PhD
University of Rochester
School of Medicine