SLSMDS Natural History Study

Study Overview
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Brief Summary
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The Single Large-Scale mtDNA Deletion Sydrome: Natural History Study (PS-NHS) aims to collect data on standardized clinical outcomes, store data on the Champ Foundation Registry (CFR) and make this data available to researchers, clinicians, and industry partners who are studying SLSMDS to answer questions regarding the disease, including its causes, potential treatments, and other topics. A secondary aim is to analyze the data to understand research questions relating to the natural history of SLSMDS.

Detailed Description
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This study is a prospective, observational, and longitudinal study intended to track the course of Pearson syndrome and single large scale mitochondrial DNA deletion syndromes (SLSMDS) to identify demographic, genetic, environmental, and other variables that correlate with the diseases development and outcomes. If available, retrospective clinical data may be accessed and used in analyses as well. The PS-NHS will be conducted at two Center of Excellence sites: the Cleveland Clinic and Children's Hospital of Philadelphia (CHOP). All PS-NHS data will be entered and stored on the CFR. The CFR exists entirely online.

Official Title
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Single Large-scale mtDNA Deletion Syndrome Natural History Study

Conditions
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Pearson Syndrome, Single Large Scale Mitochondrial DNA Deletion Syndromes (SLSMDS)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an active account on the Champ Foundation Registry (CFR) or be willing to create an account on the CFR. Must have a genetic diagnosis of a single large-scale mitochondrial DNA deletion and must upload their genetic report to the CFR. Have a clinical diagnosis or history of Pearson syndrome OR have symptom onset prior to five years of age and a genetic diagnosis of a single large-scale mitochondrial DNA deletion OR in the opinion of the principal investigator the participant is suitable for participating in this study based on clinical presentation. Participants may be of any age or gender, and originate from any country.
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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Columbia Neurological Scale | The Columbia Neurological Scale is a neurological assessment that includes a general medical exam and a general neurological exam. It will take approximately 30 minutes to complete, and that includes evaluation of nerves, muscles and movement. Columbia Neurological Scale ranges from 0 (abnormal exam) to 76 (normal exam). | 2 years | 
| PEDI-CAT assessment | The PEDI-CAT is a computerized test that will ask participants about daily life tasks. This assessment will be given to patients 0 to 20 years old and will take approximately 15 minutes to complete. | 2 years | 
| International Pediatric Mitochondrial Disease Scale | The International Pediatric Mitochondrial Disease Scale is designed to monitor general disease progression associated with mitochondrial disease in children 0 to 18 years old. It includes a physical examination and evaluation of symptoms and functioning. The International Pediatric Mitochondrial Disease Scale will include a clinician-administered assessment that involves asking participants questions and evaluating participants' movements and responses, as well as a patient survey. The score is expressed as the percentage of items which were feasible to perform. Asterixes (*) can be scored as well, the total score will change accordingly. E.g. if the parents are not able to indicate the presence of headache, the maximum score of the first domain changes from 103 to 73. If the child is not cooperative during the execution of domain 2 and 3, these items are omitted from the total score. | 2 years | 
| Scale for Assessment and Rating of Ataxia | the SARA is a physical exam that evaluates symptoms of incoordination. A physician will complete this with exam and it will take approximately 20 minutes to complete. | 2 years | 
| Balance test | Standing balance test. May assessed with an accelerometer. Measured as time in seconds. | 2 years | 
| Coordination test | 9-hold peg test. Measured as time in seconds. | 2 years | 
| 2 or 6 minute walk test | 2-minute walk test (2MWT) ages 3-6 yrs. or 6MWT (ages 6+). Measured as distance in meters. | 2 years | 
| Strength test | Hand grip with Dynamometer. Measured as average value of lbs of grip strength. | 2 years | 
| Hearing testing | Assessing hearing frequency in both ears. | 2 years | 
| EKG rhythm |  | 2 years | 
| EKG PR interval |  | 2 years | 
| EKG QRS interval |  | 2 years | 
| Echo | Assessing valve abnormalities | 2 years | 
| BNP | Measured as pg/ml | 2 years | 
| Lipid panel | Total cholesterol, HDL-C, LDL-C, triglycerides. Measured as mg/dL. | 2 years | 
| Cortisol | Measured mcg/dL | 2 years | 
| PTH | Measured as pg/mL | 2 years | 
| Calcium | Measured as pg/mL | 2 years | 
| Vitamin D | Measured ng/mL | 2 years | 
| Growth hormone | Measured ng/mL | 2 years | 
| IGF1 | Measured ng/mL | 2 years | 
| TSH | Measured uIUg/mL | 2 years | 
| FT4 and T3 | Measured ng/dL | 2 years | 
| HbA1c | Measured as a percentage | 2 years | 
| C-peptide | Measured ng/mL | 2 years | 
| Fasting Plasma Glucose (FPG) | Measured mg/dL | 2 years | 
| Fructosamine | Measured mcmol/L | 2 years | 
| Amylase | Measured U/L | 2 years | 
| Comprehensive Metabolic Panel | Electrolytes, transaminases, TP/Albumin, bilirubin, alk phos, creatinine, BUN, GFR. Measured mmol/L. | 2 years | 
| Lipase | Measured U/L | 2 years | 
| PT/PTT | Measured in seconds | 2 years | 
| Stool elastase | ug Elastase/g stool | 2 years | 
| Height | Assessed in cm | 2 years | 
| Weight | Assessed in kg | 2 years | 
| Orbitofrontal cortex (OFC) | Assessed in cm | 2 years | 
| Complete blood count with differential |  | 2 years | 
| Ferritin | Measured in ng/mL | 2 years | 
| Iron | Measured ug/dL | 2 years | 
| Reticulocytes | Count (x10^9/uL) | 2 years | 
| Reticulocytes | Percentage | 2 years | 
| Number of transfusions | Frequency count of number of red blood transfusions and platelet transfusions | 2 years | 
| Acylcarnitines (plasma) | Measured as mcmol/L | 2 years | 
| Amino acids (plasma and urine) | Interpretation recorded. | 2 years | 
| Organic acids (urine) | Interpretation recorded. | 2 years | 
| Lactate | measured mmol/L | 2 years | 
| Glutathione | Measured uM | 2 years | 
| GDF15 | pg/mL | 2 years | 
| Visual exam | Assessing palpebral fissure in mm; distance in mm; eye movement in mm | 2 years | 
| ERG/OCT | Assessed as normal or abnormal | 2 years | 
| Ptosis/ophthalmoplegia | Assessed in mm | 2 years | 
| Cystatin C | Measured mg/dL | 2 years | 
| Magnesium | Measured mg/dL | 2 years | 
| Phosphate | Measured mg/dL | 2 years | 
| Urine Electrolytes | Measured mg/dL | 2 years | 
| Urine protein | Measured mg/dL | 2 years | 
| Urine amino acids |  | 2 years | 
| Facial dysmorphology assessment | Assessed with facial photography. Assessing ptosis and/or prominent cheeks/jowls. | 2 years |