Summary
Patients with AHS and their siblings will be followed for up to 2 years. Study data will include: results of tests performed as standard of care; detailed symptom information collected through diaries; neuro-developmental test results; medical history; and supplemental clinical information. At study conclusion, study data will be summarized and relevant subgroups of Alpers syndrome patients and/or their siblings will be compared using standard statistical methods in order to identify associations between genotype and phenotype and between medical history and disease course.
Background
Alpers-Huttenlocher syndrome (AHS) is a rare autosomal recessive disorder that is characterized by seizures, liver dysfunction, and progressive developmental regression that leads to early death. Children appear healthy at birth and usually develop normally until the onset of their illness. The average onset of disease is between 2 – 4 years with smaller group of patients having onset between 17 – 24 years of age. AHS is a uniformly fatal disorder, but the rate of neurological degeneration, degree of liver involvement and age of death vary.
About this Study
This is a prospective, non-interventional, observational study. The objectives of the study are:
- To characterize the natural history of AHS stratified by POLG genotype, age of onset, sequence and timing of major symptom onset, severity and progression of organ involvement and symptom progression. If possible, we hope to identify different phenotypes of Alpers syndrome.
- To examine possible associations between specific events in patient medical history and onset of AHS, including viral illness, dehydration, fever, catabolic stress, including vaccination-related fever.
- To identify correlations between signs and symptoms of presentation of Alpers and disease severity and survival.
Target Enrollment
To be eligible to participate, you must:
The patients must fulfill the following inclusion criteria to enroll in this study.
- All individuals of any age with confirmed AHS or siblings of confirmed AHS patients are eligible to participate. AHS requires the presence of refractory seizures, developmental regression, and hepatopathy as well as two or more other clinical and laboratory findings including elevated 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 ETC enzyme deficiencies.
- All patients must agree to participate in the NAMDC Clinical Registry (7401: North American Mitochondrial Disease Consortium Patient Registry and Biorepository)
You are not eligible to participate if:
- Patient does not have confirmed AHS
- Patient not willing to participate in the NAMDC Clinical Registry
How to participate
In order to participate in a study, you may contact any of the participating sites.
Summary
The goal of this study is to find the best way to help people with primary mitochondrial disease deal with the stress of their condition, and to help these people be better able to "bounce back," or be resilient. In order to do this, the investigators are going to test two interventions (an intervention means that it aims to change something): Promoting Resilience in Stress Management (PRISM) and clinical-focused narrative (CFN) intervention.
Description
The investigators are going to test two interventions in this pilot study. The first is called Promoting Resilience in Stress Management (PRISM). The second is called clinical-focused narrative (CFN) intervention. These interventions involve talking with the researcher about several specific topics.
Participants will join six virtual study visits. They will be assigned to the PRISM group or the CFN group. During the first study visit, participants will learn about the study and will fill out consent forms if they want to participate. In the next four visits, participants will receive one of the study interventions (PRISM or CFN). Some interventions will be supported with a digital app for participants to track progress and review what was talked about in the intervention. The sixth virtual study visit will be a discussion group that happens a couple months after participants finish the intervention.
Participants will also be sent several surveys to complete. One set of surveys is sent just once after the participant enrolls in the study. Another set of surveys is sent after the participant enrolls and again after the participant finishes the interventions.
The study team will review participants' medical records to confirm they have primary mitochondrial disease and to review the genetic diagnosis. If participants do not have copies of their own medical records or if the study team does not already have access to them, the study team will ask participants to sign a release form to obtain a copy of the medical records and/or genetic testing report.
How to participate
In order to participate in a study, you may contact any of the participating sites.