Wilson's disease داء ويلسون ( التنكس الكبدي العدسي )
INSTRUCTION Look at this patient's eyes. SALIENT FEATURES History · History of consanguinity. · In young adult or child - hepatitis, haemolytic anaemia, portal hypertension or neuropsychiatric abnormalities. · In adolescents - presents as liver disease. · In adults <40 years of age consider chronic or fulminant hepatitis. Examination Greenish yellow to golden-brown pigmentation at the limbus of the cornea, called the Kayser-Fleischer ring. The ring is most marked at the superior and inferior poles of the cornea and is due to the deposition of copper in Descemet's membrane in the cornea. (It is often apparent only on slit-lamp examination. It may be absent in patients with hepatic manifestations only but is present in those with neuropsychiatric disease.) Proceed as follows: Look for the following: · Jaundice (look at the sclera). · Sunflower cataracts. · Hepatomegaly. · Signs of liver cell failure. · Neurological manifestations - tremor, chorea, mask-like facies with a vacuous smile. DIAGNOSIS This patient has a classical Kayser-Fleischer ring with jaundice and hepatomegaly (lesions) due to Wilson's disease (aetiology) and does not have a hepatic flap (functional status). ADVANCED-LEVEL QUESTIONS Is Kayser-Fleischer ring pathognomonic of Wilson's disease ? No, it is also seen in primary biliary cirrhosis, chronic active hepatitis with cirrhosis, cryptogenic cirrhosis and long-standing intrahepatic cirrhosis of childhood. At what age do the neurological manifestations usually manifest? They usually appear between 12 and 30 years of age. The most frequent first neurological symptom is difficulty in speaking or writing while in school. What do you know about the inheritance of the disease? Autosomal recessive inheritance; the gene ATP7B is located on chromosome 13, often associated with a family history of consanguinity. The disease is caused by mutations encoding a copper-transporting P-type ATPase (Wilson's disease protein, WNDP). Approximately 27 mutations have been reported; the most common, His1069Gln, is present in about a third of the patients of European extraction. What do you know about the pathophysiology of this disease? The precise detect is not known. The major aberration is excessive absorption of copper from the small intestine with decreased excretion of copper by the liver, resulting in an increase in tissue deposition, particularly in the brain, cornea, liver and kidney. The animal models of this condition are the Long-Evans cinnamon rat and the toxic milk mouse, which are currently undergoing evaluation to determine the precise detect in Wilson's disease. What are the biochemical changes in Wilson's disease? · Low serum caeruloplasmin level (caeruloplasmin is the copper-carrying protein). · Serum copper concentration may be high, low or normal. · Orally administered radiolabelled copper is incorporated into caeruloplasmin. · Increased urinary excretion of copper. How is the diagnosis of a suspected case confirmed? By the demonstration of one of the following: · Kayser-Fleischer rings and a serum caeruloplasmin level lower than 20 mg/1. · Serum caeruloplasmin concentration of less than 200 mg/I and copper concen-tration in a liver biopsy sample greater than 250 gg/g on a dry-weight basis. How would you treat such a patient? Penicillamine removes and detoxifies deposits of copper. Treatment is lifelong and continuous. What are the clinical stages of Wilson's disease? Wilson's disease progresses through four clinical stages: · Stage I: characterized by asymptomatic accumulation of copper in the liver which begins when the patient is born. * Stage II: the patient is either asymptomatic or manifests with haemolytic anaemia or liver failure. · Stage Ill: copper accumulates in the brain. · Stage IV: progressive neurological disease. Samuel Alexander Kinnier Wilson (1877-1937) qualified in Edinburgh and worked at the National Hospital, Queen Square, London, as a neurologist (Wilson SAK 1912 Progressive lenticular degeneration. A familial nervous disease associated with cirrhosis of liver. Brain 34: 295). Bernard Kayser (1869-1954) and Bruno Fleischer, both German ophthalmologists, described the same condition in 1902 and 1903 respectively.