The Myelin Disorders Biorepository Project (MDBP)

Children's Hospital of Philadelphia (CHOP)

Status: Enrolling

Conditions: Van Der Knapp Disease; Leukoencephalopathies; PMD; GM2 Gangliosidosis; Canavan Disease; AxD; X-linked Adrenoleukodystrophy; Alexanders Leukodystrophy; Refsum Disease; Vanishing White Matter Disease; Charcot-Marie-Tooth; Pelizaeus-Merzbacher Disease; Gangliosidoses; Salla Disease; Cerebrotendinous Xanthomatoses; ALSP; LCC; LBSL; Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation; 4H Syndrome; Labrune Syndrome; HCC - Hypomyelination and Congenital Cataract; AGS; Sjogren-Larsson Syndrome; Megalencephalic Leukoencephalopathy With Subcortical Cysts; Zellweger Syndrome; ALD; HBSL - Hypomyelination, Brain Stem, Spinal Cord, Leg Spasticity; X-ALD; GALC Deficiency; Alexander Disease; Metachromatic Leukodystrophy; Allan-Herndon-Dudley Syndrome; MLC1; CMT; CSF1R Gene Mutation; MLD; Globoid Leukodystrophy; Cadasil; BPAN; Mucopolysaccharidoses; H-ABC - Hypomyelination, Atrophy of Basal Ganglia and Cerebellum; ALD (Adrenoleukodystrophy); Krabbe Disease; PLP1 Null Syndrome; CTX; TUBB4A-Related Leukodystrophy; Adrenoleukodystrophy; Adrenomyeloneuropathy; Sjögren; Cockayne Syndrome; Mct8 (Slc16A2)-Specific Thyroid Hormone Cell Transporter Deficiency; ADLD; Sialic Storage Disease; Aicardi Goutieres Syndrome; Leukodystrophy; TBCK-Related Intellectual Disability Syndrome; Pelizaeus Merzbacher Like Disease; Multiple Sulfatase Deficiency; ALD Gene Mutation; HBSL; PLP1 Gene Duplication | Blood or Tissue | Mutations; White Matter Disease; Leukoencephalopathy With Brain Stem and Spinal Cord Involvement and High Lactate Syndrome (Disorder); AMN; Peroxisomal Biogenesis Disorder

Study type: Observational

Funder types: Other; Industry; NIH

Identifiers

NCT03047369

U54NS115052 (U.S. NIH Grant/Contract)

U01NS106845 (U.S. NIH Grant/Contract)

14-011236

Details and patient eligibility

About

The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago.

Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.

Full description

Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of approximately 1:7000 live births. In the past, patients with white matter disease of unknown cause evaluated by the investigator achieved a diagnosis in fewer than 46% of cases after extensive conventional clinical testing. Even when a diagnosis is achieved, the diagnosis takes an average of eight years and this "odyssey" results in testing charges to patients and insurers in excess of $8,000 on average per patient, including patients who never achieve a diagnosis at all. With next generation approaches such as whole exome sequencing, the diagnostic efficacy is closer to 70%, but approximately a third of individuals do not achieve a specific etiologic diagnosis. These diagnostic challenges represent an urgent and unresolved gap in knowledge and disease characterization, as obtaining a definitive diagnosis is of paramount importance for leukodystrophy patients.

Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood, with little known about the best symptomatic management and, thus, limited standards of care are available for the management of these patients.

The purpose of this study is to: (Aim 1) Define novel homogeneous groups of patients with unclassified leukodystrophy and work toward finding the cause of these disorders; (Aim 2) assess the validity and utility of next-generation sequencing in the diagnosis of leukodystrophies; (Aim 3) establish disease mechanisms in selected known leukodystrophies; (Aim 4) track current care and natural history of these patients to define the longitudinal course and determinants of outcomes in these disorders; (Aim 5) contact subjects for future research studies and/or clinical programs.

This biorepository will use available basic science and clinical research approaches to establish novel diagnoses, biomarkers, and outcome measures for future clinical diagnostic and therapeutic approaches.

Enrollment: 12,000 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (Affected Subjects):

• Male or female of any age;
• Suspected or confirmed diagnosis of leukodystrophy or other disorder affecting the white matter of the brain based primarily on the finding of central nervous system neuroimaging consistent with this diagnosis or on an existing diagnosis of a leukodystrophy or genetic leukoencephalopathy as defined in existing classification systems;
• Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent;
• Willingness to provide clinical data, participate in standardized assessments, and/or provide biologic samples.

Exclusion Criteria (Affected Subjects)

• Established diagnosis at the time of referral that is not consistent with a genetic disorder of the white matter, such as an acquired demyelinating condition (e.g. multiple sclerosis), or an infectious etiology, with the exception of sequelae of congenital infections such as CMV;
• Inability to provide consent.

Inclusion Criteria (Healthy Controls)

• Male or female of any age;
• Individuals with no confirmed or suspected diagnosis of leukodystrophy or other disorder affecting the white matter of the brain;
• Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent.

Exclusion Criteria (Healthy Controls)

• Inability to provide consent.