Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.

Study Overview
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Brief Summary
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General aim of the study is the improvement of the clinical knowledge of ultra-rare inherited metabolic and degenerative neurological diseases (prevalence less than 5:100,000) in adulthood through the systematic longitudinal collection of clinical, laboratory and instrumental data.

Detailed Description
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The study provides a collection of retrospective data from adult patients with ultra-rare inherited neurological diseases followed at Carlo Besta Neurological Institute from 1st January 2004 until March 2021. Further, prospective data will be collected starting from March 2021 (date of protocol approval) and spanning the next ten years. Normal clinical practice will be followed for collection of the prospective data. Follow-up assessment will be performed at least once a year to evaluate the disease course. Based on their clinical manifestations, patients will be assessed by using quantitative functional tests (clinimetric tests such as Timed Up and Go Test) and traditional ordinal scales (such as the scale for the assessment and rating of ataxia (SARA). Moreover, a varying of laboratory and instrumental tests (e.g., neuroimaging, neurophysiological investigations, etc.) will be used according to clinical practice in selected patients.

Official Title
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Clinical, Instrumental and Laboratory Data Collection of Subjects With Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases

Conditions
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Inherited Disease, Rare Diseases, Metabolic Disease, Undiagnosed Disease, Neurologic Disorder, Neuro-Degenerative Disease

Intervention / Treatment
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* Other: collection of data


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Subjects with ultra-rare inherited degenerative and metabolic neurological diseases Subjects with undiagnosed neurological diseases (when supposed to be inherited) Exclusion Criteria: none

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective study<br>collection of retrospective data from adult patients with ultra-rare inherited neurological diseases | Other: collection of data<br>* collection of retrospective and prospective data from adult patients with ultra-rare inherited neurological diseases<br>|
| Prospective study<br>prospective data will be collected starting from March 2021 (date of protocol approval) and spanning the next ten years | Other: collection of data<br>* collection of retrospective and prospective data from adult patients with ultra-rare inherited neurological diseases<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal (letter) fluency | Repeated Montreal Cognitive Assessment (MoCA) letter F fluency subtest | 10 years | 
| Stance and gait performances [Time Frame: 10 years] Stance and gait performances | Repeated SARA (Scale for the Assessment and Rating Ataxia) stance subtask, ambulation index (AI) and Timed Up and Go (TUG) test | 10 years | 
| Upper limb motor function | Repeated ONLS (Overall Neuropathy Limitation Scale) arm scale | 10 years | 
| Swallowing function (dysphagia) | Repeated NP-C mDRS (Niemann-Pick type C modified disability rating scale) swallowing scale | 10 years | 
| Speech function (dysarthria) | Repeated NP-C mDRS language scale | 10 years | 
| Bladder function | Repeated AADS (Adult Adrenoleukodystrophy Disability Score) Bladder function scale | 10 years | 
| Sleep | Repeated assessment of presence or absence of sleep disturbances | 10 years | 
| Quality of life | Repeated EuroQol-5D-5L (EQ-5D-5L) questionnaire | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukodystrophies,, Adrenoleukodystrophy,, Metachromatic leukodystrophy,, Krabbe disease,, Vanishing White Matter Syndrome,, Alexander disease,, Hereditary Leukodystrophy with Spheroids (CSF1R-related HLDS),, Nasu-Hakola disease (TREM2- and TYROBP-related disease), Leukoencephalopathy, progressive, with ovarian failure (LKENP, AARS2-related),, Pelizaeus-Merzbacher disease,, Pelizaeus-Merzbacher-like disease,, Hypomyelinating leukodystrophies,, Leukodystrophies with calcifications and cysts (LCC),, Leukoencephalopathy with ataxia disease (LKPAT, CLCN2-related),, L-2-Hydroxyglutaric aciduria,, Polyglucosan bodies disease,, Methylmalonic acidemia with homocystinuria,, Niemann-pick type C,, Fahr's disease,, Wilson's disease,, Cerebrotendinous Xanthomatosis,, Sphingolipidoses