Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort

TY - JOUR

T1 - Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort

AU - Krägeloh-Mann, I

AU - Groeschel, S

AU - Kehrer, C

AU - Opherk, K

AU - Nägele, T

AU - Handgretinger, R

AU - Müller, I

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Metachromatic leukodystrophy (MLD) is a rare inborn error of metabolism leading to severe neurological symptoms and early death. Hematopoietic SCT (HSCT) is considered a treatment option, but results are inconsistent and comparison with natural history is practically missing. We compare a girl with juvenile MLD 10 years after allogeneic HSCT not only with her untreated sister, but also with a large cohort of untreated patients. The girl received HSCT at the age of 5 years when first motor signs appeared. Over 10 years she was stable with respect to her clinical course and gained cognitive abilities. Magnetic resonance imaging (MRI) showed clear regression of white matter changes and magnetic resonance spectroscopy (MRS) demonstrated a reversal of the initial choline increase and N-acetyl-aspartate (NAA) decrease. Only axonal demyelinating neuropathy showed some progression. Her gross motor function and MRI-scores were clearly better compared with her sister and the cohort of untreated patients. Difference to her sister became apparent only 4 years after HSCT. We conclude that HSCT, early in the course of disease, can lead to stabilization of juvenile MLD with a course clearly different from the natural history. HSCT may prevent disease progression, if performed sufficient time before loss of walking, which typically initiates rapid deterioration.

AB - Metachromatic leukodystrophy (MLD) is a rare inborn error of metabolism leading to severe neurological symptoms and early death. Hematopoietic SCT (HSCT) is considered a treatment option, but results are inconsistent and comparison with natural history is practically missing. We compare a girl with juvenile MLD 10 years after allogeneic HSCT not only with her untreated sister, but also with a large cohort of untreated patients. The girl received HSCT at the age of 5 years when first motor signs appeared. Over 10 years she was stable with respect to her clinical course and gained cognitive abilities. Magnetic resonance imaging (MRI) showed clear regression of white matter changes and magnetic resonance spectroscopy (MRS) demonstrated a reversal of the initial choline increase and N-acetyl-aspartate (NAA) decrease. Only axonal demyelinating neuropathy showed some progression. Her gross motor function and MRI-scores were clearly better compared with her sister and the cohort of untreated patients. Difference to her sister became apparent only 4 years after HSCT. We conclude that HSCT, early in the course of disease, can lead to stabilization of juvenile MLD with a course clearly different from the natural history. HSCT may prevent disease progression, if performed sufficient time before loss of walking, which typically initiates rapid deterioration.

KW - Adolescent

KW - Cohort Studies

KW - Disease Progression

KW - Female

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Leukodystrophy, Metachromatic

KW - Male

KW - Treatment Outcome

U2 - 10.1038/bmt.2012.155

DO - 10.1038/bmt.2012.155

M3 - SCORING: Journal article

C2 - 22941383

VL - 48

SP - 369

EP - 375

JO - BONE MARROW TRANSPL

JF - BONE MARROW TRANSPL

SN - 0268-3369

IS - 3

ER -