Clinical trial NCT01536327: Biomarker for Metachromatic Leukodystrophy (BioMeta) Disease
Official title: Biomarker for Metachromatic Leukodystrophy Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Peripheral Neuropathy
Muscle Weakness
Keywords: leukodystrophies
Metachromatic Leukodystrophy Disease
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2012-02-22
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Metachromatic Leukodystrophy disease or profound suspicion for Metachromatic Leukodystrophy disease

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.

Eligibility criteria: INCLUSION CRITERIA:

* 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

EXCLUSION CRITERIA:

* 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

Primary outcomes:
measure: Development of a new MS-based biomarker for the early and sensitive diagnosis of metachromatic leukodystrophy disease from the blood
timeFrame: 24 month
Secondary outcomes:
measure: Testing for clinical robustness, specificity and long-term stability of the biomarker
timeFrame: 36 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Children's Hospital, Faculty of Medicine, Ain Shams University
city: Rostock
country: Germany
facility: Centogene AG
city: Cochin
country: India
facility: Amrita Institute of Medical Sciences & Research Centre
state: Kerala
city: Mumbai
country: India
facility: Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)
city: Colombo 8
country: Sri Lanka
facility: Lady Ridgeway Hospital for Children
Study officials:
affiliation: Centogene GmbH
name: Peter Bauer, Prof.
role: STUDY_CHAIR
References: