Natural History of Alpers-Huttenlocher Syndrome Study
NATURAL_HX_ALPERS
What is the goal of the study?
The purpose of this 3 year, multi-site, non-randomized, prospective, observational study is to characterize the natural history of Alpers-Huttenlocher syndrome (AHS). This syndrome is a rare autosomal recessive disease caused by mutations in the polymerase gamma 1 gene (POLG), which is responsible for all mitochondrial DNA (mtDNA) replication. POLG mutations result in reduced levels of mitochondrial DNA (mtDNA depletion), which causes loss of mitochondrial functioning and gives rise to this disorder. Disease is characterized by seizures, liver degeneration, and progressive developmental regression (Harding, 1990). Typically, children develop normally over the first few months or years with the average age at onset of 2 – 4 years, but onset can be as late as the third decade. AHS is thought to be a uniformly fatal disorder, but the rate of neurological degeneration, degree of liver involvement and age of death vary considerably. This disorder has been identified in diverse ethnic groups (Saneto et al., 2010). The study proposes to achieve the following specific aims: [Specific Aim 1] 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 AHS Syndrome. [Specific Aim 2] 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. [Specific Aim 3] To identify correlations between signs and symptoms of presentation of AHS and disease severity and survival. This study is an extension of the NAMDC Clinical Registry. 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 (Vineland II); 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. This natural history study will be one of the two initial observational studies of the North American Mitochondrial Disease Consortium (NAMDC), a NINDS-sponsored member of the Rare Disease Clinical Research Network (RDCRN) and will take advantage of the NAMDC Patient Registry, which was inaugurated in 2011. The study will creatively unite a multidisciplinary group of investigators with diverse expertise including clinical neurologists, clinical and molecular geneticists, biochemists, statisticians, and data management experts into a unique translational research team.
Who can participate in the study?
Please contact the study team listed below to learn more.