Clinical Trial: The Natural History of Metachromatic Leukodystrophy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: The Natural History of Metachromatic Leukodystrophy

Brief Summary: There have not been longitudinal studies which track patients' neurologically or developmentally in a systematic manner. By simultaneously tracking patients' neurodevelopment along with neuroimaging and neurophysiologic studies it becomes much easier to draw conclusions on the differential effects of the disease process and any available treatments that patients might receive. In addition, many of the gene mutations, which cause MLD have not been linked to the age of onset or the expected disease course.

Detailed Summary:

Metachromatic leukodystrophy (MLD), an autosomal recessively inherited lysosomal storage disorder, causes a deficiency of arylsulfatase A. This results in accumulation of sulfated glycolipids (sulphatide) within lysosomes of myelin forming cells in the central and peripheral nervous system and to a lesser extent in lysosomes of cells comprising the liver, kidneys, and gallbladder. The disease is characterized by progressive demyelination with wide variability in clinical onset and severity. Depending upon the age at onset and disease progression, MLD may be classified as late infantile (6 months to 4 years), early juvenile (4 to 6 years), late juvenile (6 to 16 years), and adult (>16 years). In the late infantile and early juvenile forms, blindness, gait disturbances, loss of speech, loss of hearing, and quadriparesis are common signs. In older children and adults the disease may present with gait disturbances, mental regression, and behavioral abnormalities. Disease progression, also variable, results in death within a few years to several decades; however, disease progression among affected siblings seems to follow a similar course, unlike many other leukodystrophies.

Bone marrow transplantation (BMT) has been the only partially effective treatment reported for MLD. BMT has been shown to halt disease progression when asymptomatic patients achieve engraftment prior to the age at which symptoms occurred in an affected, symptomatic sibling. Despite stabilization of the clinical course when receiving BMT before symptoms, patients' neurophysiologic test abnormalities persist. The clinical implication of this finding has not been further researched. Patients who show mild to moderate progression of their disease prior to transplantation continue to exhibit disease progression to severe impairment. However, specific degrees of clinical impairment in neurodevelopmental funct
Sponsor: University of Pittsburgh

Current Primary Outcome: Results of cognitive and motor testing [ Time Frame: baseline, 6 months, 12 months and then yearly ]

Patients receive standardized neurodevelopmental testing Cognitive Motor Language


Original Primary Outcome:

Current Secondary Outcome:

  • Audiology [ Time Frame: baseline, 6, 12, then yearly ]
    Audiologic examination
  • MRI [ Time Frame: yearly ]
    Magnetic Resonance Imaging of the Brain


Original Secondary Outcome:

Information By: University of Pittsburgh

Dates:
Date Received: March 11, 2008
Date Started: January 2012
Date Completion: January 2026
Last Updated: February 14, 2017
Last Verified: February 2017