Natural History Study of Patients with HPDL Mutations

NCT05848271 | Recruiting

• 1 other identifier: HPDL_NHS_001
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Mitochondrial Encephalomyopathies; Hereditary Spastic Paraplegia; Spastic Paraplegia; White Matter Disease; Neonatal Encephalopathy; Mutation; Genetic Disease

Keywords

HPDL; HPDL related neonatal mitochondrial encephalopathy; HPDL related hereditary spastic paraplegia; Spastic paraplegia-83; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities

Outcome Measures

Primary Outcomes (1)

• Clinician questionnaire

  Clinician-reported clinical and genetic confirmation of HPDL mutations

  12 months

Study Arms (1)

HPDL deficiency

Patients with HPDL mutations

Other: Patient Registry; Other: Dry blood spots sampling

Interventions

Patient Registry OTHER

Participants who have been diagnosed with HPDL mutations will be enrolled to patient registry.

HPDL deficiency

Dry blood spots sampling OTHER

Dry blood splots require 500nl of blood.

HPDL deficiency

Eligibility Criteria

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

Study Population

The gene HPDL has been linked to an infantile neurodegenerative condition. The affected patients have various clinical manifestations from spastic paraplegia to NEDSWMA. Severely affected patients exhibit developmental delay, seizures, and spasticity, and can lead to death.

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• New York University: collaborator
• Universität Tübingen: collaborator
• Heinrich-Heine University, Duesseldorf: collaborator

Study Sites (1)

Eun Hae Lee

San Diego, California, 92093, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 33188300 BACKGROUND

• 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 BACKGROUND

• 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/acn3.70047. Epub 2025 May 14.

  PMID: 40368591 DERIVED

Related Links

• website for patient registration

Biospecimen

Retention: SAMPLES WITHOUT DNA

dry blood spots

MeSH Terms

Conditions

Mitochondrial Encephalomyopathies; Spastic Paraplegia, Hereditary; Paraplegia; Leukoencephalopathies; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases; Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Joseph Gleeson

  UCSD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eun Hae Lee

CONTACT

8582460547; gleesonlab@health.ucsd.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor, neuroscience

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 8, 2023
• Study Start: May 18, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)