Michele D Poe1, Sarah L Chagnon, Maria L Escolar. 1. Program for the Study of Neurodevelopment in Rare Disorders, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
Abstract
OBJECTIVE: Hurler syndrome is the most clinically severe form of an autosomal recessive lysosomal disorder characterized by the deficiency of α-L-iduronidase. The resulting accumulation of glycosaminoglycans causes progressive multisystem deterioration, resulting in death in childhood. Umbilical cord blood transplantation from unrelated donors has been previously shown to improve neurological outcomes of children <2 years of age and prolong life. The purpose of this article is to determine whether age at transplantation can predict cognitive outcomes. METHODS: Between June 1997 and February 2013, 31 patients with Hurler syndrome underwent umbilical cord blood transplantation and were evaluated at baseline and every 6 to 12 months thereafter. All 31 patients underwent complete neurodevelopmental evaluation (median follow-up = 7.3 years, range = 2-21.7) and a median of 7.0 evaluations (range = 3-18). RESULTS: Younger age at transplantation was associated with improved cognitive function (p = 0.001), receptive and expressive language (p = 0.004 and p = 0.01), and adaptive behavior (p = 0.03). INTERPRETATION: Early age at transplantation is a strong predictor of cognitive, language, and adaptive behavior outcomes. Children younger than 9 months at the time of transplant showed normal cognitive development. Our results demonstrate that early diagnosis is necessary for optimal outcomes and support the need for newborn screening, because most patients are not identified at this young age.
OBJECTIVE:Hurler syndrome is the most clinically severe form of an autosomal recessive lysosomal disorder characterized by the deficiency of α-L-iduronidase. The resulting accumulation of glycosaminoglycans causes progressive multisystem deterioration, resulting in death in childhood. Umbilical cord blood transplantation from unrelated donors has been previously shown to improve neurological outcomes of children <2 years of age and prolong life. The purpose of this article is to determine whether age at transplantation can predict cognitive outcomes. METHODS: Between June 1997 and February 2013, 31 patients with Hurler syndrome underwent umbilical cord blood transplantation and were evaluated at baseline and every 6 to 12 months thereafter. All 31 patients underwent complete neurodevelopmental evaluation (median follow-up = 7.3 years, range = 2-21.7) and a median of 7.0 evaluations (range = 3-18). RESULTS: Younger age at transplantation was associated with improved cognitive function (p = 0.001), receptive and expressive language (p = 0.004 and p = 0.01), and adaptive behavior (p = 0.03). INTERPRETATION: Early age at transplantation is a strong predictor of cognitive, language, and adaptive behavior outcomes. Children younger than 9 months at the time of transplant showed normal cognitive development. Our results demonstrate that early diagnosis is necessary for optimal outcomes and support the need for newborn screening, because most patients are not identified at this young age.
Authors: Elsa G Shapiro; Igor Nestrasil; Kyle Rudser; Kathleen Delaney; Victor Kovac; Alia Ahmed; Brianna Yund; Paul J Orchard; Julie Eisengart; Gregory R Niklason; Julian Raiman; Eva Mamak; Morton J Cowan; Mara Bailey-Olson; Paul Harmatz; Suma P Shankar; Stephanie Cagle; Nadia Ali; Robert D Steiner; Jeffrey Wozniak; Kelvin O Lim; Chester B Whitley Journal: Mol Genet Metab Date: 2015-06-17 Impact factor: 4.797
Authors: Ryan D Geraets; Seung yon Koh; Michelle L Hastings; Tammy Kielian; David A Pearce; Jill M Weimer Journal: Orphanet J Rare Dis Date: 2016-04-16 Impact factor: 4.123