Early diagnosis benefits patients
A recent paper in New England Journal of Medicine reinforces the importance of early diagnosis for effective treatment in LSD.
Escolar et al (NEJM 352:30, 2069-2081, 2005) transplanted babies with infantile Krabbe’s disease with umbilical cord blood. They compared engraftment, survival and neurodevelopmental function in 11 asymptomatic newborns, transplanted between 12-44 days old with 14 infants ages 142-352 days, diagnosed after onset of symptoms. Survival at 3 years follow up was 100% in the asymptomatic newborns compared with 43% in the symptomatic infants.
The asymptomatic newborns showed progressive central myelination and continued development, cognitive function and language skills, in comparison with the children undergoing transplantation after the onset of symptoms, who showed minimal neurological improvement.
Comment by the study’s senior author, Joanne Kurtzburg MD, Director, Duke University Pediatric Blood and Marrow Transplant Program:
"Cord blood transplantation in newborns with LSDs saves lives and prevents the otherwise terrible neurological sequelae of these diseases. Newborns tolerate the therapy better than older children, Cord blood donors are readily available and can be identified within a few days of birth. Mandatory newborn screening should be implemented so that babies can be diagnosed and treated before significant brain damage occurs."
LSDs are best treated if patients are diagnosed and treated in early infancy – before the symptoms of the disease become apparent. If the child is transplanted after onset of symptoms, there is an increased (though significantly less than if transplanted presymptomatically) chance of survival over untreated children, but little improvement in neurological development. Timing is critical to the successful development of motor skills. Source of stem cells is also important. Cord blood provides a better and faster correction of enzyme deficiency than adult bone marrow, and UBC stem cells repair deficiencies in central and peripheral nervous systems.
Similar results have been observed in treatment of Hurler syndrome (MPS I)
In this study, the presymptomatic infants were diagnosed due to a family history of Krabbe disease. Newborn screening would identify babies with no family history of the disease, and effective treatment could prevent the devastating results of Krabbe and other LSD.
Krabbe disease (Globoid cell leukodystrophy) is an autosomal recessive LSD caused by mutation in the galactosylceramidase gene (GALC) located on chromosome 14. Over 60 mutations have been identified. Deficiency of the enzyme galactocerebrosidase prevents the processing of galactolipids found in myelin, the sheath of nerve axons. Failure of myelination in central and peripheral nervous systems leads to rapidly progressive neurological deterioration.
Classically, Krabbe disease presents in early infancy, with irritability, crying, spasms, dysphagia, deafness, blindness, arrested motor function, developmental delay and hyperpyrexia. The disease is rapidly progressive with loss of bulbar function. Death usually occurs at approximately 12-18 months.
For more information on Krabbe Disease visit:
GOLD - Disease Information search
United Leukodystrophy Foundation
Hunter's Hope Foundation
National Niemann-Pick Disease Foundation