Browsing by Subject "Leukodystrophy, Metachromatic"

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    Gallbladder abnormalities in children with metachromatic leukodystrophy.
    (The Journal of surgical research, 2017-02) Kim, Jina; Sun, Zhifei; Ezekian, Brian; Schooler, Gary R; Prasad, Vinod K; Kurtzberg, Joanne; Rice, Henry E; Tracy, Elisabeth T

    Background

    Metachromatic leukodystrophy (MLD) is a lysosomal storage disease that leads to neurological deterioration and visceral involvement, including sulphatide deposition in the gallbladder wall. Using our institution's extensive experience in treating MLD, we examined the incidence of gallbladder abnormalities in the largest cohort of children with MLD to date.

    Methods

    We conducted a retrospective review of all children with MLD, adrenoleukodystrophy (ALD), or Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) at our institution between 1994 and 2015. Baseline characteristics and unadjusted outcomes were compared using the Kruskal-Wallis test for continuous variables and Pearson χ2 test for categorical variables, with significance defined as P < 0.05.

    Results

    In total, 87 children met study criteria: 29 children with MLD and 58 children with ALD or Krabbe disease. Children with MLD were more likely to demonstrate gallbladder abnormalities on imaging, both before HSCT (41.4% versus 5.2%, P < 0.001) and after HSCT (75.9% versus 41.4%, P = 0.002). Consequently, a larger proportion of children with MLD underwent surgical or interventional management of biliary disease (10.3% versus 3.4%, P = 0.03).

    Conclusions

    Children with MLD have a significantly greater incidence of gallbladder abnormalities than children with other lysosomal storage diseases. Biliary disease should be considered in children with MLD who develop abdominal pain, and cholecystectomy should be considered for persistent, symptomatic gallbladder abnormalities.
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    Gene therapy offers new hope for children with metachromatic leukodystrophy.
    (Lancet (London, England), 2022-01) Kurtzberg, Joanne
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    Hematopoietic Stem Cell Transplantation to Treat Leukodystrophies: Clinical Practice Guidelines from the Hunter's Hope Leukodystrophy Care Network.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2019-12) Page, Kristin M; Stenger, Elizabeth O; Connelly, James A; Shyr, David; West, Tara; Wood, Susan; Case, Laura; Kester, Maureen; Shim, Soo; Hammond, Lauren; Hammond, Matthew; Webb, Christin; Biffi, Alessandra; Bambach, Barbara; Fatemi, Ali; Kurtzberg, Joanne
    The leukodystrophies are a heterogeneous group of inherited diseases characterized by progressive demyelination of the central nervous system leading to devastating neurologic symptoms and premature death. Hematopoietic stem cell transplantation (HSCT) has been successfully used to treat certain leukodystrophies, including adrenoleukodystrophy, globoid leukodystrophy (Krabbe disease), and metachromatic leukodystrophy, over the past 30 years. To date, these complex patients have primarily been transplanted at a limited number of pediatric centers. As the number of cases identified through pregnancy and newborn screening is increasing, additional centers will be required to treat these children. Hunter's Hope created the Leukodystrophy Care Network in part to create and standardize high-quality clinical practice guidelines to guide the care of affected patients. In this report the clinical guidelines for the care of pediatric patients with leukodystrophies undergoing treatment with HSCT are presented. The initial transplant evaluation, determination of patient eligibility, donor selection, conditioning, supportive care, and post-transplant follow-up are discussed. Throughout these guidelines the need for early detection and treatment and the role of the partnership between families and multidisciplinary providers are emphasized.
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    Leukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry.
    (Analytical chemistry, 2020-05) Hong, Xinying; Kumar, Arun Babu; Daiker, Jessica; Yi, Fan; Sadilek, Martin; De Mattia, Fabiola; Fumagalli, Francesca; Calbi, Valeria; Damiano, Roberta; Della Bona, Maria; la Marca, Giancarlo; Vanderver, Adeline L; Waldman, Amy T; Adang, Laura; Sherbini, Omar; Woidill, Sarah; Suhr, Teryn; Kurtzberg, Joanne; Beltran-Quintero, Maria L; Escolar, Maria; Aiuti, Alessandro; Finglas, Alan; Olsen, Amber; Gelb, Michael H
    Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were developed to measure arylsulfatase A (ARSA) activity in leukocytes and dried blood spots (DBS) using deuterated natural sulfatide substrate. These new assays were highly specific and sensitive. Patients with metachromatic leukodystrophy (MLD) and multiple sulfatase deficiency (MSD) displayed a clear deficit in the enzymatic activity and could be completely distinguished from normal controls. The leukocyte assay reported here will be important for diagnosing MLD and MSD patients and for monitoring the efficacy of therapeutic treatments. ARSA activity was measured in DBS for the first time without an antibody. This new ARSA DBS assay can serve as a second-tier test following the sulfatide measurement in DBS for newborn screening of MLD. This leads to an elimination of most of the false positives identified by the sulfatide assay.
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    Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2013-04) Martin, Holly R; Poe, Michele D; Provenzale, James M; Kurtzberg, Joanne; Mendizabal, Adam; Escolar, Maria L
    Metachromatic leukodystrophy (MLD) is an inherited demyelinating disease that causes progressive neurologic deterioration, leading to severe motor disability, developmental regression, seizures, blindness, deafness, and death. The disease presents as a late-infantile, juvenile, or adult form. Hematopoietic stem cell transplantation has been shown to slow disease progression. The purpose of this longitudinal study was to evaluate long-term treatment outcomes after unrelated donor umbilical cord blood (UCB) transplantation in pediatric patients according to disease burden and age at onset (ie, late-infantile versus juvenile). Engraftment, survival, treatment-related toxicity, graft-versus-host disease, neurophysiologic measures, and neurodevelopmental function were assessed. To evaluate whether signal intensity abnormalities on magnetic resonance imaging (ie, modified Loes scores) predict post-transplant cognitive and gross motor development, a general linear mixed model was fit to the data. Twenty-seven patients underwent transplantation after myeloablative chemotherapy; 24 patients engrafted after the initial transplantation. Seven patients died of infection, regimen-related toxicity, or disease progression. Twenty patients (6 with late-infantile onset and 14 with juvenile onset) were followed for a median of 5.1 years (range, 2.4 to 14.7). We found that patients with motor function symptoms at the time of transplant did not improve after transplantation. Brainstem auditory evoked responses, visual evoked potentials, electroencephalogram, and/or peripheral nerve conduction velocities stabilized or improved in juvenile patients but continued to worsen in most patients with the late-infantile presentation. Pretransplant modified Loes scores were highly correlated with developmental outcomes and predictive of cognitive and motor function. Children who were asymptomatic at the time of transplantation benefited most from the procedure. Children with juvenile onset and minimal symptoms showed stabilization or deterioration of motor skills but maintained cognitive skills. Overall, children with juvenile onset had better outcomes than those with late-infantile onset. As in other leukodystrophies, early intervention correlated with optimal outcomes. We conclude that UCB transplantation benefits children with presymptomatic late-infantile MLD or minimally symptomatic juvenile MLD.