Clinical trial NCT05848271: Natural History Study of Patients with HPDL Mutations
Official title: A Patient Registry and Natural History Study of Patients with Biallelic HPDL Mutations
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: New York University
name: Universität Tübingen
name: Heinrich-Heine University, Duesseldorf
First posted: 2023-05-08
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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

Primary outcomes:
measure: Clinician questionnaire
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Eun Hae Lee
state: California
Study officials:
affiliation: UCSD
name: Joseph Gleeson
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.