Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies

NCT03056794 | Recruiting DMC

• 2 other identifiers: STUDY210901465U54NS078059-05
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Children and adults with pyruvate dehydrogenase complex deficiency (PDCD) are participating in a research study seeking to better understand the genetic causes, symptoms, usefulness of current treatments, and outcomes for these disorders. The research project involves completing a questionnaire about the individual or family's medical history and experiences with PDCD, review of medical records by the researchers, and in some cases, advanced genetic testing.

Conditions

Pyruvate Dehydrogenase Complex Deficiency Disease

Keywords

pyruvate; pyruvate dehydrogenase; PDC; PDCD

Outcome Measures

Primary Outcomes (1)

• Survival outcomes in pyruvate dehydrogenase deficiency disease

  Survival will be measured in years and months.

  Data will be collected about duration of survival from birth until the last date known to be living at the time of data analysis.

Secondary Outcomes (1)

• Neurological outcomes in pyruvate dehydrogenase deficiency disease

  Through a participant questionnaire and retrospective review of medical records, neurological outcomes will be assessed for the entire lifetime of the participant up to the time of data collection.

Study Arms (1)

PDC Deficiency

Pyruvate Dehydrogenase Complex Deficiency Disease

Other: No intervention

Interventions

No intervention OTHER

This is an observational study. The investigators will collect data about exposure to responses to dietary supplements, medications, and the ketogenic diet.

PDC 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

Children and adults with pyruvate dehydrogenase complex deficiency

You may qualify if:

• Low PDC activity in skin fibroblasts, blood lymphocytes or a muscle biopsy, below the reference range, and with valid internal controls to establish sample and assay integrity, and have had PDHA1 testing, and/or
• A known pathogenic mutation of a gene associated with PDC deficiency.
• \. First or second degree relative of a primary subject for whom genetic testing indicates the presence of variants of unknown significance (VUS).

You may not qualify if:

• Another chronic neurological disease (mitochondrial or non-mitochondrial) which is not considered likely to be related to PDC deficiency.
• Inadequacy of needed blood or tissue sample and unwillingness or inability to submit such a sample.
• Unwillingness to participate in the NAMDC Patient Data Registry and Biorepository protocol.
• \. Inadequacy of needed blood sample and unwillingness or inability to submit such a sample.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

RECRUITING

Related Publications (7)

• DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab. 2012 Nov;107(3):394-402. doi: 10.1016/j.ymgme.2012.09.001. Epub 2012 Sep 7.

  PMID: 23021068 BACKGROUND

• Huang X, Bedoyan JK, Demirbas D, Harris DJ, Miron A, Edelheit S, Grahame G, DeBrosse SD, Wong LJ, Hoppel CL, Kerr DS, Anselm I, Berry GT. Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion. Mol Genet Metab. 2017 Mar;120(3):213-222. doi: 10.1016/j.ymgme.2016.11.005. Epub 2016 Nov 12.

  PMID: 27913098 BACKGROUND

• Bedoyan JK, Yang SP, Ferdinandusse S, Jack RM, Miron A, Grahame G, DeBrosse SD, Hoppel CL, Kerr DS, Wanders RJA. Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Apr;120(4):342-349. doi: 10.1016/j.ymgme.2017.02.002. Epub 2017 Feb 2.

  PMID: 28202214 BACKGROUND

• Ferdinandusse S, Friederich MW, Burlina A, Ruiter JP, Coughlin CR 2nd, Dishop MK, Gallagher RC, Bedoyan JK, Vaz FM, Waterham HR, Gowan K, Chatfield K, Bloom K, Bennett MJ, Elpeleg O, Van Hove JL, Wanders RJ. Clinical and biochemical characterization of four patients with mutations in ECHS1. Orphanet J Rare Dis. 2015 Jun 18;10:79. doi: 10.1186/s13023-015-0290-1.

  PMID: 26081110 BACKGROUND

• Deeb KK, Bedoyan JK, Wang R, Sremba L, Schroeder MC, Grahame GJ, Boyer M, McCandless SE, Kerr DS, Zhang S. Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. Mol Genet Metab Rep. 2014 Aug 28;1:362-367. doi: 10.1016/j.ymgmr.2014.08.001. eCollection 2014.

  PMID: 27896109 BACKGROUND

• Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JK. Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Nov;122(3):61-66. doi: 10.1016/j.ymgme.2017.09.001. Epub 2017 Sep 8.

  PMID: 28918066 BACKGROUND

• Bedoyan JK, Hecht L, Zhang S, Tarrant S, Bergin A, Demirbas D, Yang E, Shin HK, Grahame GJ, DeBrosse SD, Hoppel CL, Kerr DS, Berry GT. A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. JIMD Rep. 2019 Jun 17;48(1):26-35. doi: 10.1002/jmd2.12054. eCollection 2019 Jul.

  PMID: 31392110 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample for DNA and biochemical analysis. Saliva, buccal swab, urine sample, blood sample, or skin sample for NAMDC biorepository (optional).

MeSH Terms

Conditions

Pyruvate Dehydrogenase Complex Deficiency Disease

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Study Officials

• Jirair K. Bedoyan, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jirair K Bedoyan, MD, PhD

CONTACT

412-692-7594; bedoyanjk@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: February 17, 2017
• Study Start: September 1, 2015
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)