Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) in the 18th Century: Mitochondrial Disorders Are Not of Recent Origin.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome was one of the first mitochondrial disorders to be identified and characterized, being described as early as 1984. The clinical manifestations of MELAS vary but stroke-like episodes are a defining feature. Mutations in at least 17 mitochondrial DNA (mtDNA) located genes have been shown to be associated with this disorder. Mary Ann, the youngest child of Josiah and Sarah Wedgwood, was born in August 1778 when Sarah was aged 44 years. Mary Ann was of short stature and was physically and mentally retarded. She suffered from partial and generalized seizures and episodes of cortical blindness. She died at the age of eight years. Descriptions of her illness remain and she is depicted with disabilities as can be seen in a family portrait. Her illness is consistent with MELAS. The illnesses of her elder siblings and of their mother are in keeping with a maternally inherited pathological mtDNA mutation, supporting this diagnosis. Her illness is the key to the remarkable illnesses that affected the Wedgwood family. Through her eldest sibling, Susannah, married to Robert Darwin, the disorder was passed to the next generation, a generation that included Charles Darwin and his elder brother, Erasmus.