Content area
Full Text
Abstract
Hepatolenticular degeneration (Wilson's disease) is a rare genetic disorder with various presentations that can be quite challenging to the clinician. The defect in the hepatic copper-transporting ATPase gene (ATP7B) leads to copper metabolism dysfunction and copper accumulation in various tissues. Classic presentations include liver disease, neuropsychiatric manifestations, and corneal Kayser-Fleischer rings. First described in 1854 by German pathologist, Friedrich Theodor von Frerichs (1819-1885), the initial definitive description was provided in 1912 by British neurologist Samuel Alexander Kinnier Wilson (1878-1937). This paper provides current understanding of Wilson disorder: its history, genetics, pathophysiology, diagnosis, and management.
Keywords: Pediatrics, Wilson's disease, genetics
Introduction
Wilson's disease, also called hepatolenticular degeneration, is an unusual autosomal-recessive disorder due to tissue copper accumulation in various tissues related to malfunction of the gene ATP7B (copper transporting P-type ATPase) (1-4). Its global prevalence is noted with various estimates as 1 in 50 to 10,000 live births as well as 1 in 30,000; such calculations can vary from population to population and with the sensitivity of screening tools that are utilized (3, 4).
The most common presentations are chronic liver disease, neuropsychiatric disorders and/or Kayser-Fleischer rings; though involvement of the liver and brain (basal ganglia) are the most common, other organ dysfunction may occur as well (1-6). Clinical presentation of Wilson's disease can vary considerably in children as well as adults and early diagnosis is needed to blunt its potential dangerous effects (5, 6). Considered in this discussion of Wilson's disease are its eponymous history, genetics, pathophysiology, diagnosis, and principles of management.
Historical perspectives
Initial understanding of neurological disorders can be attributed to such early scholars as the English physician Gilbertus Anglicus (1180-1250 AD) who distinguished between epilepsy and stroke in addition to the English physician, John of Gaddesden (1280-1361-who authored a comprehensive publication on medicine called the Compendium of Medicine (Compendium Medicinae) (2, 7). The study of brain diseases is often attributed to the father of neurology, British anatomist/physician Thomas Willis (1621-1675), who wrote seven medical books including his famous 1664 Cerebri anatome (2, 8-10).
The first description of what would later be called Wilson's disease is attributed to the famous German pathologist, Friedrich Theodor von Frerichs (18191885) in 1854 (2, 11-13). Kayser-Fleischer rings found in the iris are named after the...