Alpers Huttenlocher Natural History Study (Alpers)

Natural History Study of Alpers Huttenlocher Syndrome

This is a natural history study of Alpers Huttenlocher Syndrome. Patients will be followed over time to assess clinical symptoms for the purpose of expanding knowledge of this disorder in the medical community.

Study Overview

• Status: Terminated
• Conditions: Alpers Huttenlocher Syndrome

Detailed Description

The study team will conduct outpatient visits to the medical center on a 6 month basis, or as patients are able. The patients or their caregivers will complete medical and symptom questionnaires.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with Alpers Huttenlocher Syndrome (AHS) and their siblings

Description

Inclusion Criteria:

• All individuals of any age with confirmed Alpers Huttenlocher Syndrome (AHS) or siblings of confirmed AHS patients are eligible to participate. AHS requires the presence of polymerase gamma 1 (POLG) pathological mutations, either homozygous or compound heterozygote mutations, and the presence of epilepsy and either, developmental regression or hepatopathy. If POLG mutations are not demonstrated, AHS requires the presence of refractory seizures, developmental regression, and hepatopathy as well as two or more other clinical and laboratory findings including elevated cerebrospinal fluid (CSF) protein, neuroimaging showing lactate peaks, reduced N-acetyl aspartate with hyperintensities on T2/FLAIR in the thalamus and posterior head regions, optic atrophy/cortical blindness, quantitative mtDNA reduction (>30% ) in muscle and/or liver, non-specific electron transport chain (ETC) enzyme deficiencies.
• All patients must agree to participate in the North American Mitochondrial Disease Consortium (NAMDC) Clinical Registry

Exclusion Criteria:

• Patient does not have confirmed AHS and is not the sibling of a patient with confirmed AHS
• Not willing to participate in the NAMDC clinical Registry

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with Alpers-Huttenlocher; Patients confirmed to have Alpers Huttenlocher Syndrome
Siblings; Siblings of patients with Alpers Huttenlocher Syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
onset age	age at onset of first symptom versus POLG mutation type	2 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Seattle Children's Hospital
• Investigators: Study Chair: Russell Saneto, MD, Seattle Children's Hospital

Publications and helpful links

Helpful Links

• North American Mitochondrial Disease Consortium (NAMDC) Study Site

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): July 27, 2022

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (Estimate): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease; Leukoencephalopathies; Syndrome; Diffuse Cerebral Sclerosis of Schilder
• Other Study ID Numbers: AAAM9859; 2U54NS078059-04 (U.S. NIH Grant/Contract); 5U54NS078059-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: This study is a sub project under the North American Mitochondrial Disease Consortium. The de-identified data can be shared if investigators have Institutional Review Board (IRB) approval for a project that might include data from this study and if the NAMDC administration approves of the project

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No