Natural History Study of SLC25A46 Mutation-related Mitochondriopathy

NCT04594590 | Completed DMC

• 1 other identifier: STUDY00004513-SLC
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to systematically characterize the clinical course of the progressive neuropathy and optic atrophy observe in pediatric and adult patients with biallelic mutations in the solute carrier family 25 member 46 (SLC25A46) gene.

Conditions

Neurodegenerative Disease, Hereditary; Mitochondrial Diseases; Optic Atrophy

Keywords

Neurodegeneration; Mitochondrial disease; Optic atrophy; SLC25A46; Mitochondrial fission

Outcome Measures

Primary Outcomes (6)

• Custom Medical History Questionnaire for Patients with SLC25A46 Mutation-related Mitochondriopathy

  In addition to a standard medical history, patients or their legal guardians will be asked to complete a custom medical history questionnaire tailored toward conditions commonly observed in patients with biallelic SLC25A46 mutations. The items that will be asked about in this questionnaire are as follows: 1. Known mutations in SLC25A46 2. Any family history of illness 3. Complications of pregnancy 4. Premature birth 5. Complications with birth 6. Developmental delay 7. Developmental regression 8. Abnormal size of brain 9. Movement disorders (ataxia, dystonia, etc.) 10. Seizures 11. Optic atrophy in eye exam 12. Vision loss 13. Other vision problems (color, eye movement) 14. Hypotonia (muscle weakness or lack of tone) 15. Electromyogram (EMG) 16. Muscle biopsy 17. Spasticity (muscle stiffness or tightness) 18. Brain MRI performed? 19. Electroencephalogram (EEG)

  3 years

• Retrospective examination of the medical records of patients with SLC25A46 Mutation-related Mitochondriopathy

  With the informed consent of the patients or their parent(s) and/or legal guardian(s), the investigators will perform a retrospective examination of the medical records of both living and deceased patients with confirmed biallelic SLC25A46 mutations.

  3 years

• Eye assessments to evaluate ocular health

  Visual acuity examination will be performed to determine the patient's clarity or sharpness of vision.

  3 years

• Growth and development (height)

  World Health Organization (WHO) growth charts will be used to document height in centimeters (cm) for patients ranging from ages 5 to 19 years old. Routine methods will be used to document height for all other age groups.

  3 years

• Growth and development (weight)

  World Health Organization (WHO) growth charts will be used to document weight in kilograms (kg) for pediatric patients age 5 to 10 years old. Routine methods will be used to document weight for all other age groups.

  3 years

• Growth and development (BMI)

  World Health Organization (WHO) growth charts will be used to document Body Mass Index (BMI) in kilograms per meter square for patients age 5 to 19 years old. Routine methods will be used to document BMI for all other age groups.

  3 years

Study Arms (1)

Patients with SLC25A46 deficiency

Male and female patients from age 2 to age 65 with clinically confirmed SLC25A46 mutations. Both living and deceased patients will be included, if eligible. For deceased patients, the patient's medical history records will be reviewed, and an interview of the parent(s) or caregiver(s) will be performed.

Genetic: Mutation analysis

Interventions

Mutation analysis GENETIC

The investigators will sequence DNA samples from the patients or their families.

Patients with SLC25A46 deficiency

Eligibility Criteria

• Age: 0 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic

You may qualify if:

• Patients who are clinically diagnosed with biallelic mutations in the SLC25A46 gene
• Male and female patients from 2 to 65 years of age
• Patients who have consented to the study
• In the case of a deceased patient whose parent(s) and/or legal guardian(s) have provided informed consent for study participation, the investigators will review the patient's medical records to determine study eligibility.

You may not qualify if:

• Significant postnatal complications or congenital anomalies that are not known to be associated with SLC25A46 dysfunction
• Patient has received any experimental treatment for SLC25A46 dysfunction within the 6 months prior to enrollment, or is expected to receive any such therapy during the study period

Sponsors & Collaborators

• State University of New York at Buffalo: lead
• Hadley Jo Foundation: collaborator

Study Sites (1)

UBMD Pediatrics

Buffalo, New York, 14203, United States

Location

Related Publications (5)

• Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schule R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Nemeth AH, Carelli V, Huang T, Zuchner S, Dallman JE. Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Nat Genet. 2015 Aug;47(8):926-32. doi: 10.1038/ng.3354. Epub 2015 Jul 13.

  PMID: 26168012 BACKGROUND

• Li Z, Peng Y, Hufnagel RB, Hu YC, Zhao C, Queme LF, Khuchua Z, Driver AM, Dong F, Lu QR, Lindquist DM, Jankowski MP, Stottmann RW, Kao WWY, Huang T. Loss of SLC25A46 causes neurodegeneration by affecting mitochondrial dynamics and energy production in mice. Hum Mol Genet. 2017 Oct 1;26(19):3776-3791. doi: 10.1093/hmg/ddx262.

  PMID: 28934388 BACKGROUND

• Yang L, Slone J, Li Z, Lou X, Hu YC, Queme LF, Jankowski MP, Huang T. Systemic administration of AAV-Slc25a46 mitigates mitochondrial neuropathy in Slc25a46-/- mice. Hum Mol Genet. 2020 Mar 13;29(4):649-661. doi: 10.1093/hmg/ddz277.

  PMID: 31943007 BACKGROUND

• Qiu K, Zou W, Fang H, Hao M, Mehta K, Tian Z, Guan JL, Zhang K, Huang T, Diao J. Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts. Nat Commun. 2022 Jul 25;13(1):4303. doi: 10.1038/s41467-022-31970-5.

  PMID: 35879298 BACKGROUND

• Zou W, Chen Q, Slone J, Yang L, Lou X, Diao J, Huang T. Nanoscopic quantification of sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells derived from patients with mitochondrial diseases. J Nanobiotechnology. 2021 May 13;19(1):136. doi: 10.1186/s12951-021-00882-9.

  PMID: 33985528 BACKGROUND

Related Links

• Link to the official website for the "Hadley Jo Foundation"

Biospecimen

Retention: SAMPLES WITH DNA

The medical records will be retained for all patients. For select patients, blood, DNA, skin punch biopsies will also be obtained for the purpose of genetic and biochemical analysis

MeSH Terms

Conditions

Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Optic Atrophy; Nerve Degeneration

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Taosheng Huang

  State University of New York at Buffalo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 20, 2020
• Study Start: November 3, 2020
• Primary Completion: August 17, 2023
• Study Completion: August 17, 2023
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)