Natural History Study of Patients With HPDL Mutations

Genetic Disease Clinical Trial

Official title:

A Patient Registry and Natural History Study of Patients With Biallelic HPDL Mutations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05848271
• Other study ID #: HPDL_NHS_001
• Status: Recruiting
• Start date: May 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2023
• Source: University of California, San Diego
• Contact: Eun Hae Lee
• Phone: 8582460547
• Email: gleesonlab[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study uses medical records that allow retrospective data extraction of clinical manifestation to assess the natural history of HPDL mutations

Description:

A novel mitochondrial disease arises from mutations in HPDL, which codes for 4-hydroxyphenylpyruvate dioxygenase-like protein. The main purpose of this study is to establish a patient registry to gather medical data from consenting HPDL mutation patients worldwide. From longitudinal data, we will be able to figure out the natural history of the disease, and genotype-phenotype correlation. Dry blood spots will be collected to develop biomarkers to understand the disease better.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Any individuals diagnosed with HPDL variants
• Clinical diagnosis can include:
• HPDL-related hereditary spastic paraplegia (HSP)
• HPDL-related neonatal mitochondrial encephalopathy
• Spastic paraplegia -83 (SPG83)
• Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA)

Exclusion Criteria:

• Any known genetic abnormality (other than HPDL mutation)
• Any condition that, in the opinion of the Site Investigator, could put the participant at undue risk and/or would ultimately prevent the completion of study procedures

Related Conditions & MeSH terms

• Brain Diseases
• Genetic Disease
• Genetic Diseases, Inborn
• Hereditary Spastic Paraplegia
• Leukoencephalopathies
• Mitochondrial Encephalomyopathies
• Muscle Spasticity
• Mutation
• Neonatal Encephalopathy
• Paraplegia
• Spastic Paraplegia
• Spastic Paraplegia, Hereditary
• White Matter Disease

Intervention

Other:
• Patient Registry
Participants who have been diagnosed with HPDL mutations will be enrolled to patient registry.
• Dry blood spots sampling
Dry blood splots require 500nl of blood.

Locations

Country	Name	City	State
United States	Eun Hae Lee	San Diego	California

Sponsors (4)

Lead Sponsor	Collaborator
University of California, San Diego	Heinrich-Heine University, Duesseldorf, New York University, Universität Tübingen

Country where clinical trial is conducted

United States, 

References & Publications (2)

Banh RS, Kim ES, Spillier Q, Biancur DE, Yamamoto K, Sohn ASW, Shi G, Jones DR, Kimmelman AC, Pacold ME. The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. Nature. 2021 Sep;597(7876):420-425. doi: 10.1038/s41586-021-03865-w. Epub 2021 Sep 1. — View Citation

Ghosh SG, Lee S, Fabunan R, Chai G, Zaki MS, Abdel-Salam G, Sultan T, Ben-Omran T, Alvi JR, McEvoy-Venneri J, Stanley V, Patel A, Ross D, Ding J, Jain M, Pan D, Lubbert P, Kammerer B, Wiedemann N, Verhoeven-Duif NM, Jans JJ, Murphy D, Toosi MB, Ashrafzadeh F, Imannezhad S, Karimiani EG, Ibrahim K, Waters ER, Maroofian R, Gleeson JG. Biallelic variants in HPDL, encoding 4-hydroxyphenylpyruvate dioxygenase-like protein, lead to an infantile neurodegenerative condition. Genet Med. 2021 Mar;23(3):524-533. doi: 10.1038/s41436-020-01010-y. Epub 2020 Nov 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinician questionnaire	Clinician-reported clinical and genetic confirmation of HPDL mutations	12 months

External Links

•   website for patient registration