Biomarker for Metachromatic Leukodystrophy (BioMeta) Disease

Withdrawn

• Conditions: Peripheral Neuropathy; Muscle Weakness

• Registration Number: NCT01536327
• Lead Sponsor: CENTOGENE GmbH Rostock

Brief Summary

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

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 Timeline

• Study First Submitted: 2012-02-21
• Study First Submitted QC: 2012-02-21
• Study First Posted: 2012-02-22
• Study Start: 2018-08-20
• Primary Completion: 2021-02-28
• Study Completion: 2021-02-28
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-09
• Last Update Posted: 2023-02-13

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Development of a new MS-based biomarker for the early and sensitive diagnosis of metachromatic leukodystrophy disease from the blood	24 month	New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

Secondary Outcome Measures

Name	Time	Method
Testing for clinical robustness, specificity and long-term stability of the biomarker	36 months	the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

Trial Locations

Locations (5)

Centogene AG; 🇩🇪 Rostock, Germany

Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN); 🇮🇳 Mumbai, India

Children's Hospital, Faculty of Medicine, Ain Shams University; 🇪🇬 Cairo, Egypt

Amrita Institute of Medical Sciences & Research Centre; 🇮🇳 Cochin, Kerala, India

Lady Ridgeway Hospital for Children; 🇱🇰 Colombo 8, Sri Lanka