An observational study in Mitochondrial, Leukoencephalopathies and Leukoencephalopathy, sponsored by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta. Recruiting at 1 site in Italy. Per ClinicalTrials.gov, last updated 2026-10-09.
Sponsored by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta · Observational
Mitochondrial disorders (MDs) are among the most common inherited metabolic diseases, caused by genetic defects in mitochondrial or nuclear DNA that impair cellular energy production. The central nervous system (CNS) is frequently affected, due to its high energy demands. Within the broad clinical spectrum of MDs, mitochondrial leukoencephalopathies (MLs) have emerged as a distinct subgroup characterized by CNS white matter involvement.
MLs are clinically and genetically heterogeneous, with onset ranging from infancy to adulthood. Patients may experience episodes of neurological regression, often triggered by stressors such as febrile illnesses, alongside variable motor, cognitive, and occasionally extraneurological involvement. Neuroimaging typically reveals diffuse or focal white matter abnormalities, including cavitation and rarefaction, with additional involvement of deep gray matter structures. Certain ML subtypes exhibit characteristic MRI patterns that may aid in diagnosis.
Despite recent advancements in the genetic and neuroradiological characterization of MLs, significant knowledge gaps persist. Although the number of disease-causing genes has increased over the last decades, a comprehensive understanding of genotype-phenotype correlations is still lacking. Additionally, knowledge on the natural history of these disorders is limited. Existing data often focus on imaging findings with insufficient integration of clinical, biochemical, and molecular features, limiting the understanding of disease mechanisms, progression, and therapeutic responses.
In light of these gaps, this multicenter, observational, retrospective study aims to systematically collect and analyze clinical, biochemical, neuroradiological, and genetic data from individuals with MLs, assessed at international reference centers for MDs. The study seeks to better elucidate the phenotypic variability and genotype-phenotype correlations of MLs. This work is expected to enhance diagnostic accuracy, inform management strategies, support prognostic counseling, and ultimately contribute to the better overall management of affected individuals
39 studies on the registry are indexed under Leukoencephalopathies; 16 are open to participants now.
This study's planned enrollment of 100 is close to the median of 100 across 28 observational studies indexed under Leukoencephalopathies.
Browse Leukoencephalopathies studies →Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta is the lead sponsor of 84 studies on the registry; 32 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patient with a confirmed genetic diagnosis of mitochondrial leukoencephalopathy
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Confirmed diagnosis of ML, confirmed by:
Exclusion Criteria:
Unconfirmed diagnosis of mitochondrial leukoencephalopathy , including cases where:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Comprehensive characterization of genotype-phenotype correlations in MLs.
The primary endpoint for evaluating the principal objective of this study is the comprehensive characterization of genotype-phenotype correlations in MLs. This will be assessed through the collection and analysis of retrospective longitudinal clinical, neuroradiological and genetic data. Clinical phenotypes will then be stratified based on specific underlying genetic defects, assessing their impact on disease onset and progression to establish robust genotype-phenotype correlations. Data collection will include: * Family history, including inheritance patterns and consanguinity when applicable. * Age at symptom onset * Initial clinical presentation, documenting key symptoms and signs at disease onset. * Progression of disease manifestations, capturing the evolution of neurological and extraneurological features over time. * Neuroradiological findings, assessed through MRI scans to evaluate white matter abnormalities, other signal abnormalities or specific MRI findings
Time frame: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data: NMDAS
Disease progression in adults assessed by the Newcastle Mitochondrial Disease Adult Scale (NMDAS) Disease severity and progression in adult participants will be assessed using the Newcastle Mitochondrial Disease Adult Scale (NMDAS). Unit of Measure: NMDAS total score.
Time frame: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data: Serum lactate levels
Serum lactate levels will be collected and analyzed, when available, to characterize biochemical abnormalities and their changes over time Unit of Measure: nmol/h/mg.
Time frame: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data. : Serum pyruvate levels
Serum pyruvate levels will be collected and analyzed, when available, to characterize biochemical abnormalities and their changes over time Unit of Measure: nmol/h/mg.
Time frame: 12 months
Change in disease severity in treated adult participants assessed by NMDAS
In adult participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in disease severity will be assessed using the Newcastle Mitochondrial Disease Adult Scale (NMDAS), when available. Unit of Measure: NMDAS total score
Time frame: 12 months
Change in disease severity in treated pediatric participants assessed by NPMDS
In pediatric participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in disease severity will be assessed using the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS), when available. NPMDS total score
Time frame: 12 months
Change in serum lactate levels in treated participants
In participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in serum lactate levels will be assessed, when available. Unit of Measure: Serum lactate concentration
Time frame: 12 months
Change in serum pyruvate levels in treated participants
In participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in serum pyruvate levels will be assessed, when available. Unit of Measure: Serum pyruvate concentration
Time frame: 12 months
Progression of brain MRI abnormalities in treated participants
In participants receiving disease-specific therapeutic interventions as part of their clinical care, available longitudinal brain MRI examinations will be evaluated for progression of neuroradiological abnormalities. Unit of Measure: Percentage of participants with radiological progression
Time frame: 12 months
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta