title: Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy.
abstract: OBJECTIVE
  Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder due to deficient activity of arylsulfatase A (ASA) that causes accumulation of sulfatide and lysosulfatide. The disorder is associated with demyelination and axonal loss in the central and peripheral nervous systems. The late infantile form has an early-onset, rapidly progressive course with severe sensorimotor dysfunction. The relationship between the degree of nerve damage and (lyso)sulfatide accumulation is, however, not established.
  
  
  METHODS
  In 13 children aged 2-5 years with severe motor impairment, markedly elevated cerebrospinal fluid (CSF) and sural nerve sulfatide and lysosulfatide levels, genotype, ASA mRNA levels, residual ASA, and protein cross-reactive immunological material (CRIM) confirmed the diagnosis. We studied the relationship between (lyso)sulfatide levels and (1) the clinical deficit in gross motor function (GMFM-88), (2) median and peroneal nerve motor and median and sural nerve sensory conduction studies (NCS), (3) median and tibial nerve somatosensory evoked potentials (SSEPs), (4) sural nerve histopathology, and (5) brain MR spectroscopy.
  
  
  RESULTS
  Eleven patients had a sensory-motor demyelinating neuropathy on electrophysiological testing, whereas two patients had normal studies. Sural nerve and CSF (lyso)sulfatide levels strongly correlated with abnormalities in electrophysiological parameters and large myelinated fiber loss in the sural nerve, but there were no associations between (lyso)sulfatide levels and measures of central nervous system (CNS) involvement (GMFM-88 score, SSEP, and MR spectroscopy).
  
  
  CONCLUSIONS
  Nerve and CSF sulfatide and lysosulfatide accumulation provides a marker of disease severity in the PNS only; it does not reflect the extent of CNS involvement by the disease process. The magnitude of the biochemical disturbance produces a continuously graded spectrum of impairments in neurophysiological function and sural nerve histopathology.
authors.affiliation: Department of Clinical Genetics, Rigshospitalet Copenhagen, Denmark.
authors.forename: Christine Í
authors.initials: CÍ
authors.lastname: Dali
authors.affiliation: Shire Lexington, Massachusetts.
authors.forename: Norman W
authors.initials: NW
authors.lastname: Barton
authors.affiliation: Department of Neurology, Johns Hopkins Medical Institutions Baltimore, Maryland.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Farah
authors.affiliation: Department of Clinical Neurophysiology, Rigshospitalet Copenhagen, Denmark ; Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.
authors.forename: Mihai
authors.initials: M
authors.lastname: Moldovan
authors.affiliation: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital Gothenburg, Sweden.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Månsson
authors.affiliation: Shire Lexington, Massachusetts.
authors.forename: Nitin
authors.initials: N
authors.lastname: Nair
authors.affiliation: Department of Clinical Genetics, Rigshospitalet Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Dunø
authors.affiliation: Department of Clinical Genetics, Rigshospitalet Copenhagen, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Risom
authors.affiliation: Shire Lexington, Massachusetts.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Cao
authors.affiliation: Shire Lexington, Massachusetts.
authors.forename: Luying
authors.initials: L
authors.lastname: Pan
authors.affiliation: Shire Lexington, Massachusetts.
authors.forename: Marcia
authors.initials: M
authors.lastname: Sellos-Moura
authors.affiliation: Department of Neurology, Johns Hopkins Medical Institutions Baltimore, Maryland.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Corse
authors.affiliation: Department of Clinical Neurophysiology, Rigshospitalet Copenhagen, Denmark ; Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Krarup