Long-Term Functional Outcomes after Hematopoietic Stem Cell Transplant for Early Infantile Krabbe Disease

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) can retard the progression of early infantile Krabbe disease (EIKD). Superior outcomes are achieved if HSCT is performed before the onset of symptoms; however, little information is available about the long-term outcomes in surviving patients. We now describe functional outcomes in presymptomatic infants who underwent HSCT for EIKD at ≤ 2 months of age. Records of the 19 patients who underwent HSCT for EIKD at ≤ 2 months of age from 1996 to 2010 were reviewed. Long-term functional outcomes were compared between those transplanted at < 30 days and ≥ 30 days of life. Median age at transplant was 27 days (range, 19 to 61). Median follow-up of the cohort was 12.6 years. Overall survival at 5 and 10 years post-transplant was 84.2% (95% confidence interval, 58.7% to 94.6%) and 78.6% (95% confidence interval, 52.5% to 91.4%), respectively. More favorable outcomes were seen in patients who underwent HSCT at < 30 days of age, particularly in domains of mobility (P = .01), communication (P = .02), and feeding (P = .008). Improved functional outcomes were observed when HSCT was performed in the first month of life, defining a critical period for intervention. These results support the implementation of newborn screening to enable rapid diagnosis and early treatment of infants with EIKD.

Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease

“…While GALC should intuitively be required during myelination, many of these temporal events seem to precede the bulk of CNS myelination. Furthermore, patients diagnosed in utero, and treated within the first few weeks of life, do better than patients treated at 1–2 months old 12 , 13 . These findings underlie the necessity for properly defining the precise timepoint in which GALC is first required.…”

Family Attitudes regarding Newborn Screening for Krabbe Disease: Results from a Survey of Leukodystrophy Registries

“…NBS for a leukodystrophy known as Krabbe disease (KD) started in New York state in 2006, soon after it was shown that early cord blood transplantation favorably alters the natural history of the disease [ 1 , 2 , 3 ]. NBS for KD was added to additional state panels after New York (Illinois, Indiana, Kentucky, Louisiana, Missouri, New Jersey, New Mexico, Ohio, Pennsylvania, South Carolina, Tennessee), and KD NBS has started in Indiana, Kentucky, Missouri, New Jersey, New York, Ohio, Illinois and Tennessee.…”

“…The first five early infantile KD NBS-positive patients in New York state had several factors leading to a delay in treatment, which negatively impacted patient outcomes [ 4 ]. Long-term follow-up of KD patients identified via family history who were treated by hematopoietic stem cell transplantation have been published [ 1 , 7 , 8 ]. Furthermore, new data on treated patients identified through NBS will be reported in the near future, which show improved outcomes since the first eight years in New York.…”

“…Long-term follow-ups of KD patients identified via family history who were treated by hematopoietic stem cell transplantation have been published [ 1 , 7 , 8 ]. Data on treated patients identified through NBS will be reported in the near future and show a similar outcome to patients identified early through family history.…”

Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders

“…Interestingly, psychosine accumulation is neurotoxic and has been reported to facilitate fibrillation of α-synuclein (SNCA) [99,100,103]. There is still no effective treatment for Krabbe disease, but stem cell transplant has been a modality of treatment in some states of the USA [104].…”