Clinical and Translational Perspectives on WILSON DISEASE

Nanda Kerkar,Eve A Roberts

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128105337
• Topic: Medicina
• Subtopic: Gastroenterología y hepatología

Clinical and Translational Perspectives on Wilson Disease brings together the genetics, cell and structural biology of Wilson Disease into one contemporary, easy to navigate handbook. Created to meet the diverse needs of the clinical and research communities surrounding Wilson Disease, this reference provides a worldwide approach that is concise and translational. Specifically, it provides a basis for clinicians to appreciate 'basic science' aspects of Wilson disease, presenting a guide for researchers to understand the clinical disorder on which their research is focused and fostering constructive dialogue and progress for this puzzling disorder.

• Delivers numerous, succinct, expert chapters with summaries designed for quick reference
• Includes a 'How-to appendix' for diagnosis and management tips
• Contains access to a companion website with a self-help teaching module, links to key resources, and an extended reference list

Chapter 1

A History of Wilson Disease

Stuart Tanner, Sheffield Children's Hospital (Division of Child Health), University of Sheffield, Sheffield, United Kingdom

Abstract

Wilson disease was first described as “progressive lenticular degeneration” by Samuel Alexander Kinnear Wilson in 1912; however, earlier reports may date back to 1860. Over the next several decades, the connection with cirrhosis, including in children, was appreciated. By the mid-century, the critical role of copper in the pathogenesis of this disease was generally recognized. Bearn showed that it was an autosomal disorder in 1960, although previous investigators had surmised as much decades earlier. Research into the biochemistry of ceruloplasmin in the 1950s connected this protein with Wilson Disease (WD), with various false leads along the way. Pharmacological treatments developed between 1950 and 1980 revolutionized the clinical management of WD. The gene was identified in 1993, and this contributed to an explosion of knowledge about copper physiology across the phyla.

Keywords

Wilson disease; copper; history; Kayser–Fleischer ring; ceruloplasmin; gene; pseudosclerosis; hepatolenticular degeneration

Introduction: Finding a New Disease

In 1906, Sir William Gowers published detailed case histories of a 10-year-old boy and his 15-year-old sister, who were affected by a neurodegenerative condition characterized by athetosis and dystonia and who at autopsy were found to have hepatic cirrhosis [1]. He had previously described “tetanoid chorea with cirrhosis” in his 1888 textbook. In his classic 1912 monograph [2], Wilson cited these cases from 1888 as the first two recorded cases of the disease he was describing in detail. Whether these were the first published cases of ATP7B deficiency or whether that honor goes to Westphal and Strümpell who in 1883 and 1898, respectively, described patients with “pseudosclerosis” (tremor resembling multiple sclerosis without the eye signs) remains arguable [3]. Joseph Ormerod described a patient with cirrhosis and softening of the lenticular nucleus in 1890. Even earlier, a similar case is found in the New Sydenham Society translation of Friedrich Theodor von Frerichs’ Clinical treatise on diseases of the liver in 1860. In an addendum to his monograph, Wilson alluded tangentially to the Westphal–Strümpell pseudosclerosis disorder by way of allowing that a patient described by Völsch in 1911 resembled what Wilson was describing more closely than it resembled what Westphal–Strümpell had described. Certainly, whatever its precedents, the disease described by Wilson was to remain almost exclusively a neurological disease for the next half-century. This is despite the paper by Sir Byrom Bramwell in 1916 [4] describing four of seven children in the same family who died at ages 9, 10, 14, and 14 years old, respectively, of cirrhosis presenting with acute deterioration, though not necessarily fitting the description of classic Wilsonian acute liver failure. He suggested a relationship to Wilson's progressive lenticular degeneration of which the childhood hepatic form might be a forme fruste and suggested that it was a genetic disease. Fifty years later, Chalmers and colleagues writing about WD pointed out the need to investigate copper in all cases of cirrhosis in childhood [5].

The clinical and basic science research relating to Wilson disease (WD) spans the 20th century. Table 1.1 shows a timeline of discovery in Wilson disease.

Table 1.1

A Timeline of Discovery in Wilson Disease

1878	Samuel Alexander Kinnier Wilson born
1883 and 1898	Pseudosclerosis described by Westphal and Strümpell
1888	Gowers: “tetanoid chorea with cirrhosis”
1902 and 1903	Kayser and Fleischer describe the pigmented corneal ring independently
1911	SAKW's MD with gold medal
1912	SAKW's Brain paper: progressive lenticular degeneration with cirrhosis
1913	Rumpel finds increased liver copper
1916	Bramwell describes childhood hepatic form
1920s	SAKW's film made at Queen Square
1921	Hall: hepatolenticular degeneration; autosomal recessive inheritance (confirmed 1960)
1923	Familial cases of childhood liver disease and later neurological abnormality
1930	Haurowitz reported increased liver copper
1937	SAKW dies
1945	Glazebook: raised brain copper
1947	Laurell: ceruloplasmin
1948	Mandelbrote shows cupriuretic effect of BAL
1948	Cumings: suggests BAL may be a diagnostic procedure and a treatment
1951	Treatment with BAL reported by Denny-Brown (United States) and Cumings (United Kingdom)
1952	Serum ceruloplasmin shown to be low in WD
1955	Penicillamine given to first patient
1958	Menghini needle
1961	Schouwink reports use of zinc
1969	Trientine as alternative oral chelator
1970s	Radiocopper studies
1971	First liver transplant in WD
1984	Walshe describes use of tetrathiomolybdate
1978	Wilson Disease Association founded in New York
1985	Frydman ascribes WD gene locus to chromosome 13
1986	The Nazer score
1990–94	Reports of haplotype diagnosis of WD
Jan 1993	3 Groups report gene abnormal in Menkes disease
Dec 1993	3 Groups report gene abnormal in WD
1995	Aceruloplasminemia
1997	Wilson ATPase protein expressed
2004	EuroWilson consortium
2005	Revised King’s score

SAKW, Samuel Alexander Kinnier Wilson; BAL, British anti-Lewisite.

Samuel Alexander Kinnier Wilson (SAKW) 1878–1937

At the Wilson’s Disease Centennial Symposium in October 2012, Dr. Edward Reynolds showed part of a remarkable film made by Samuel Alexander Kinnier Wilson (SAKW) in the 1920s. Reynolds described [6] meeting SAKW’s younger son James in 1987 at a symposium to commemorate the 50th anniversary of SAKW’s death and subsequently in 2006 his grandson who had stored in his attic “an old medical film” made by his grandfather. The 20-minute silent film shows 14 neurological patients, mostly filmed on the pavement outside The National Hospital, Queen Square, including a 25-year-old woman with progressive lenticular degeneration, showing severe tremor, rigidity, and abnormal gait. Reynolds speculated that the high quality of the film, made on 1924 USA Kodak film with state-of-the-art technology including slow-motion sequences, is attributable to SAKW’s friendship with Charlie Chaplin. Possibly SAKW’s influence is seen in the hysterical paralysis of the leading lady’s legs in Chaplin’s movie “Limelight.”

SAKW was born in New Jersey but grew up in Scotland following the death of his father. He graduated MB in 1902 and BSc Physiology in 1903 from Edinburgh. He then studied under the eminent neurologist Pierre Marie in Paris, as well as in Leipzig, before becoming House Physician at the National Hospital for the Paralysed and Epileptic, Queen Square, in London. He remained there as Resident Medical Officer, Registrar, Pathologist, Assistant Physician, and, finally, full Physician (1921) and also held appointments at Westminster and King’s College Hospitals.

He obtained his MD with gold medal at Edinburgh in 1911; his MD thesis was the basis for his seminal 212-page paper in Brain entitled “Progressive lenticular degeneration, a familial nervous disease associated with liver cirrhosis,” published the following year [2].

The following abbreviated extract from the opening paragraphs of the paper (pages 296–7) summarizes its scope.

THE object of this paper is to give a full description of a rare nervous disease … to which … the name of “Progressive Lenticular Degeneration” may be conveniently applied. The disease is familial but not hereditary; it may also occur sporadically. It occurs always in young people, either in an acute or a chronic form. … It is progressive and invariably fatal, its duration ranging from six months to five years. The clinical symptoms form a complex which … may be considered to be a pure syndrome of the corpus striatum. In a word, it consists of involuntary movements, nearly always a bilateral ...