Biomarker for Metachromatic Leukodystrophy Disease (BioMeta)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01536327
Recruitment Status : Not yet recruiting
First Posted : February 22, 2012
Last Update Posted : August 28, 2018
Information provided by (Responsible Party):
Centogene AG Rostock

Brief Summary:
Development of a new MS-based biomarker for the early and sensitive diagnosis of Metachromatic Leu-kodystrophy disease from blood (plasma)

Condition or disease
Peripheral Neuropathy Muscle Weakness

Detailed Description:

Metachromatic Leukodystrophy Disease (MLD) is one of a group of genetic disorders called the leukodystrophies. These diseases impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers. Myelin, which lends its colour to the white matter of the brain, is a complex substance made up of varying lipids (75%) and proteins (25%). The leukodystrophies are caused by genetic defects in myelin production or metabolization of the compounds of the myelin sheath. Each of the leukodystrophies is the result of a defect in the gene that controls one (and only one) of the enzymes responsible for creating or degrading a part of the myelin. MLD is caused by a deficiency of the enzyme arylsulfatase A. MLD is one of several lipid storage diseases, which results in the toxic build-up of fatty materials (lipids) in cells in the nervous system, liver, and kidneys. There are three forms of MLD: late infantile, juvenile, and adult. Onset of the late infantile form (the most common MLD) is typically between 12 and 20 months following birth. Affected children have difficulty walking after the first year of life. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Most children with this form of MLD die by age 5. The juvenile form of MLD (between 3-10 years of age) usually begins with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the infantile form but with slower progression. The adult form commonly begins after age 16 as a psychiatric dis-order or progressive dementia. Symptoms include impaired concentration, ataxia, seizures, dementia, and tremor. Due to consanguinity autosomalrecessive disorders such as MLD have higher prevalence in Arabian countries.

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow to diagnose in the future the disease earlier, with a higher sensitivity and specificity. In a pilotstudy glycosylsphingosin-sulfatid has been determined as a sensitive and specific biomarker. This is a metabolic product likely to be involved in the pathophysiology of the disease. Therefore it is the goal of the study to validate this new biochemical marker from the blood (plasma) of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment. Examining blood samples will allow to determine whether measurement of the identified marker lyso-Gb1-Sulfatid is feasible in blood samples and will further promote early detection of MLD.

Though MLD is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is elevated in countries with a higher frequency of consanguinity. Therefore, we estimate that every 400th newborn in Arabian countries may be eligible for inclusion due to high-grade suspicion of MLD, while approximately every 2000th newborn in a non-Arabian country may be eligible.

Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Metachromatic Leukodystrophy Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Patients with Metachromatic Leukodystrophy disease or profound suspicion for Metachromatic Leukodystrophy disease

Primary Outcome Measures :
  1. Development of a new MS-based biomarker for the early and sensitive diagnosis of metachromatic leukodystrophy disease from the blood [ Time Frame: 24 month ]

Secondary Outcome Measures :
  1. Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 24 month ]

Biospecimen Retention:   Samples With DNA

For the development of the new biomarkers using the technique of mass-spectometry, 10 ml EDTA blood sample and/or a dry blood spot filter card-blood sample will be taken from the patient. To prove the correct Metachromatic Leukodystrophy diagnosis in those patients where up to the enrolment in the study no genetic testing has been done, sequencing of Metachromatic Leukodystrophy will be done as routine diagnostic.

The analyses will be done at the:

Centogene AG Am Strande 7 18055 Rostock Germany

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Metachromatic Leukodystrophy disease or profound suspicion for Metachromatic Leukodystrophy disease


  • Informed consent will be obtained from the patient or the parents before any study related procedures
  • Patients from one day
  • The patient has a diagnosis of Metachromatic Leukodystrophy disease or profound suspicion for Metachromatic Leukodystro-phy disease
  • High-grade suspicion present, if one or more criteria are valid:

Positive family anamnesis for MLD

Neurologic symptoms of unknown origin: peripheral neuropathy, clumsiness, choreatiform movements, spastic quadriplegia, loss of ambulation, bulbar dysfunction/paresis, dysphagia, seizure disorders

Psychiatric symptoms of unknown origin: mental regression, emotional la-bility, disorganized thinking or hallucinations/delusions

Muscle symptoms of unknown origin: muscle weakness


  • No Informed consent from the patient or the parents before any study related procedures
  • No diagnosis of MLD or no valid criteria for high-grade suspicion of MLD

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01536327

Contact: Anton Mamin, Dr. +49 381 80113 535
Contact: Volha Skrahina +49 381 80 113 594

Pediatric practice Not yet recruiting
Oran, Algeria, 31000
Contact: Abdelmadjid Benmansour, MD   
Principal Investigator: Abdelmadjid Benmansour, MD         
University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration Not yet recruiting
Rostock, Germany, 18147
Contact: Susanne Zielke    +49 381 494 ext 4739   
Principal Investigator: Arndt Rolfs, Prof.         
NIRMAN, University of Mumbai Not yet recruiting
Mumbai, India, 400705
Contact: Anil Jalan, MD   
Principal Investigator: Anil Jalan, MD         
Sponsors and Collaborators
Centogene AG Rostock
Principal Investigator: Arndt Rolfs, Prof. Centogene AG Rostock

Additional Information:
Responsible Party: Centogene AG Rostock Identifier: NCT01536327     History of Changes
Other Study ID Numbers: BMLD 06-2018
First Posted: February 22, 2012    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Centogene AG Rostock:
Metachromatic Leukodystrophy Disease

Additional relevant MeSH terms:
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Peripheral Nervous System Diseases
Muscle Weakness
Leukodystrophy, Metachromatic
Neuromuscular Diseases
Nervous System Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Hereditary Central Nervous System Demyelinating Diseases
Central Nervous System Diseases
Lysosomal Storage Diseases, Nervous System
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders