Early Diagnosis and Cord Blood Transplantation Prevents Permanent Brain Damage From Rare Inherited Disease, Children’s Hospital of Pittsburgh of UPMC Study Finds

November 19, 2014

PITTSBURGH, PA - November 19, 2014 - Umbilical cord blood from unrelated donors can halt the progression of the neurodegenerative disease Hurler syndrome if performed before the affected child is less than 9 months old, according to aChildren's Hospital of Pittsburgh of UPMC study that appears online in Annals of Neurology. The findings emphasize the need for early diagnosis of the condition, preferably through newborn screening programs.

Hurler syndrome is the most clinically severe form of an inherited disorder in which the patient lacks a key enzyme needed to break down complex sugars called glycosaminoglycans. The sugar buildup results in progressive organ deterioration and death in childhood. Affected children may not have symptoms until age 3, but the brain undergoes damage before symptoms present.

Umbilical cord blood transplantation from unrelated donors has previously been shown to improve neurological outcomes of children over 2 years of age and prolong life. Hematopoietic stem cells from the cord blood transplants provide a source for the normal enzyme that is donated to the deficient cells decreasing the accumulation of gycosaminoglycans.

Key findings of this study show that treatment of Hurler syndrome with umbilical cord blood transplantation before 9 months of age leads to normal cognitive development. The researchers found children transplanted at 12 and 25 months of age functioned cognitively at a level 2 to 5.3 years below that of those transplanted at 4 months. Early transplantation also predicted better outcomes for language skills and adaptive behaviors.

"The purpose of the study was to determine whether age at transplantation can predict cognitive outcomes," said Maria Luisa Escolar, MD, MS, director, Program for the Study of Neurodevelopment in Rare Disorders, Children's Hospital, and associate professor of pediatrics, University of Pittsburgh School of Medicine. "This study highlights the importance of early detection of brain diseases in babies and infants when brain growth is the most accelerated in life, placing them at increased vulnerability for permanent damage."

Between June 1997 and February 2013, 31 children with Hurler syndrome underwent umbilical cord blood transplantation and were evaluated every six to 12 months thereafter for an average of seven years. Median age at transplantation was 13.8 months. The youngest babies in the study were diagnosed due to family history of the condition.

"Identification of asymptomatic children through statewide newborn screening programs is the only way to diagnose early and prevent brain damage to babies with no family history of Hurler syndrome," Dr. Escolar said.

"Unfortunately, early diagnosis is often difficult as their initial symptoms may be common in the general population," added Dr. Escolar. "Therefore, there is a need for newborn screening for Hurler syndrome and similar neurodegenerative diseases that can identify children before symptoms appear, giving the best opportunity for prompt intervention and optimal outcomes."

Collaborators with Dr. Escolar on the study were Michele Poe, PhD, and Sarah Chagnon, MD, both with Children's Hospital of Pittsburgh of UPMC.

Financial support for this work was received from the Caterina Marcus Foundation.

For more information on Dr. Escolar and the Program for the Study of Neurodevelopment in Rare Disorders, visit www.chp.edu/ndrd.

Andrea Kunicky, 412-692-6254, andrea.kunicky@chp.edu  

Marc Lukasiak, 412-692-7919, marc.lukasiak@chp.edu