7405: Natural History of Alpers-Huttenlocher Syndrome

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:

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 Alpers syndrome.
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.
3. 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.

1. 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.
2. 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:

1. Patient does not have confirmed AHS
2. 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.