Natural History Study of Patients with HPDL Mutations
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Patient Registry, Dry blood spots sampling.
- Who it may be relevant to
- Registry conditions: Mitochondrial Encephalomyopathies, Hereditary Spastic Paraplegia, Spastic Paraplegia, White Matter Disease. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Patient Registry and Natural History Study of Patients with Biallelic HPDL Mutations
Overview
This study uses medical records that allow retrospective data extraction of clinical manifestation to assess the natural history of HPDL mutations
Detailed 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.
Interventions
- Other Patient Registry
Participants who have been diagnosed with HPDL mutations will be enrolled to patient registry. - Other Dry blood spots sampling
Dry blood splots require 500nl of blood.
Primary outcome measures
- Clinician questionnaire [Time frame: 12 months]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 1 center
- Eun Hae Lee — San Diego
Publications
- 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 diox PMID 33188300
- 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. PMID 34471290
- Lee EH, Kim-Mcmanus O, Yang JH, Haas R, Zaki MS, Abdel-Salam GMH, Nakamura Y, Abdel-Hamind MS, Ebrahimi-Fakhari D, Alecu JE, Brunetti-Pierri N, Srinivasan VM, Gowda VK, Gross S, Alanay Y, Najarzadeh Totbati P, Yadavilli M, Friedman L, Ojeda NM, Gleeson JG. HPDL Variant Type Correlates With Clinical Disease Onset and Severity. Ann Clin Transl Neurol. 2025 Jul;12(7):1360-1367. doi: 10.1002/acn3.7004 PMID 40368591
Identifiers
NCT: NCT05848271 · HPDL_NHS_001