Wilson-Conovalov disease - Symptoms.

The symptoms of Wilson-Konovalov disease are characterized by diversity, which is due to the damaging effect of copper on many tissues. The predominant damage to one or another organ depends on age. In children, this is mainly the liver (hepatic forms). Later, neurological symptoms and mental disorders (neuropsychic forms) begin to prevail. If the disease manifests itself after 20 years, then patients usually have neurological symptoms. A combination of symptoms of both forms is possible. Most patients aged 5 to 30 years already have clinical manifestations of the disease or a diagnosis has been made.

Liver forms

Fulminant hepatitis is characterized by progressive jaundice, ascites, liver and kidney failure and usually develops in children or young adults. Liver cell necrosis is associated primarily with copper accumulation. In almost all patients, hepatitis develops against the background of cirrhosis. Sudden massive release of copper from dead hepatocytes into the blood can cause acute intravascular hemolysis. Hemolysis of this type has been described in sheep with copper poisoning, as well as in humans with accidental copper poisoning.

The Kayser-Fleischer ring may be absent. Urine and serum copper levels are very high. Serum ceruloplasmin levels are usually low. However, they may be normal or even elevated because ceruloplasmin is an acute phase reactant that increases in concentrations during active liver disease. Serum transaminase and alkaline phosphatase levels are significantly lower than in fulminant hepatitis. A low alkaline phosphatase/bilirubin ratio, although not diagnostic of fulminant hepatitis in Wilson disease, may nevertheless suggest its possibility.

Chronic hepatitis. Wilson's disease may present with the picture of chronic hepatitis: jaundice, high transaminase activity and hypergammaglobulinemia. The age of patients at the time of appearance of these symptoms is 10-30 years. Neurological symptoms appear approximately after 2-5 years. The picture of the disease may largely resemble other forms of chronic hepatitis, which emphasizes the need to exclude Wilson's disease in all patients with chronic hepatitis.

Cirrhosis. Latent disease at the stage of liver cirrhosis may manifest itself with vascular asterisks, splenomegaly, ascites, portal hypertension. Neurological symptoms may be absent. In some patients, cirrhosis is compensated. For its diagnosis, a liver biopsy may be required, if possible with a quantitative determination of copper content in the biopsy.

Wilson's disease should be considered in all young patients with chronic liver disease who have mental disturbances (eg, slurred speech, early development of ascites or hemolysis), especially if there is a family history of cirrhosis.

Hepatocellular carcinoma is very rare in Wilson's disease; copper may play a protective role.

Neuropsychic forms

Depending on the predominant symptoms, there are parkinsonian, pseudosclerotic, dystonic (dyskinetic) and choreic forms (listed in order of decreasing frequency). Neurological symptoms may appear acutely and progress rapidly. Early symptoms include flexor-extensor tremor of the hands, facial muscle spasms, difficulty writing, slurred speech. Inconstant rigidity of the limbs is detected. Intelligence is usually preserved, although 61% of patients show manifestations of a slowly progressive personality disorder.

Neurological disorders are often chronic. They begin at a young age with a large-scale tremor, reminiscent of a wing flap, which intensifies with voluntary movements. There are no sensory disturbances or symptoms of damage to the pyramidal tract. The face is amimic. In patients with a severe dystonic form, the prognosis is comparatively worse.

Electroencephalography reveals generalized nonspecific changes that may also be observed in clinically healthy siblings of the patient.

Kidney damage

Renal tubular damage occurs as a result of copper deposition in their proximal sections and is manifested by aminoaciduria, glucosuria, phosphaturia, uricosuria, and the inability to excrete para-aminohippurate.

Renal tubular acidosis is common and can lead to stone formation.

Other changes

Rarely, copper deposits cause the lunulae to become blue. Osteoarticular changes include bone demineralization, early osteoarthrosis, subarticular cysts, and periarticular bone fragmentation. Spine changes due to calcium pyrophosphate dihydrate deposition are common. Hemolysis promotes gallstone formation. Copper deposits result in hypoparathyroidism. Acute rhabdomyolysis associated with high skeletal muscle copper levels has been described.

In the later stages of the disease, copper is deposited at the edge of the cornea as a golden or greenish-gold Kayser-Fleischer ring, visible with a slit lamp. It is usually seen in patients with neurological symptoms and may be absent in young patients with an acute onset of the disease.

A similar ring is sometimes found in prolonged cholestasis and cryptogenic cirrhosis of the liver.

Rarely, "sunflower"-shaped, grayish-brown cataracts may develop in the posterior layer of the lens capsule, similar to those seen in copper-containing lens foreign bodies.

Without timely initiation of treatment, lifelong and continuous treatment, the disease leads to death before reaching the age of thirty.