Edison

Friedreich’s Ataxia (FRDA)

Friedreich’s ataxia is an autosomal nuclear DNA (nDNA) inherited disease, affecting an estimated 50,000 individuals worldwide. Friedreich’s’ ataxia is caused by a defect in the gene frataxin. Frataxin is a 210-amino acid protein that participates in iron-sulfur cluster protein assembly. Individuals with Friedreich’s Ataxia have defects in proteins containing Fe-S clusters. As the majority of these Fe-S cluster proteins are localized to the respiratory chain in the mitochondria, patients with Friedreich’s ataxia present with “energy failure” symptoms including heart failure, ataxia, diabetes, and visual and hearing deficiencies. There are no approved drugs for Friedreich’s ataxia.

Mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS)

MELAS is a mitochondrial DNA (mtDNA) inherited disease, with an unknown prevalence. There are over 15 different point mutations in the mtDNA genome that can give rise to MELAS, however the A3243G mutation accounts for approximately 80% with an estimated prevalence of 1-16/100,000. MELAS is usually diagnosed early in life. The mechanism whereby the A3243G mutation leads to the clinical presentation of MELAS is unknown. The clinical presentation is diverse. Signs and symptoms include exercise intolerance; lactate production at rest; stroke and seizures, hearing and visual disturbances; and dementia. There are no treatments for MELAS, and a high likelihood that, as with other inherited mitochondrial diseases, the prevalence of disease may be substantially higher. The prognosis for MELAS patients is poor. Individuals with MELAS generally do not live beyond young adulthood.

Leber’s Hereditary Optic Neuropathy (LHON)

Leber’s hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) inherited disease, with a prevalence of between 1:30-50,000. The syndrome of LHON is predominately caused by one of three point mutations in NADH dehydrogenase subunits contained in complex I. LHON is clinically manifested by visual disturbances that lead to blindness secondary to retinal ganglion cell injury and death. The mechanisms whereby complex I defects lead to blindness are uncertain. Males are affected in a greater proportion than females; primary in their 20’s. Approximately 50% of male and 85% of female LHON carriers do not clinically convert. While it is known that tobacco and alcohol may precipitate conversion, other secondary factors such as nDNA genes may be involved. There are no treatments for LHON, and a high likelihood that, as with other inherited mitochondrial diseases, the prevalence of disease may be substantially higher.