Wilson-Konovalov disease: diagnosis

The Kaiser-Fleischer ring is easily detected during normal inspection (70%) or by a slit lamp (97%). Specificity of this feature for hepatolenticular degeneration is more than 99%.

The most accurate laboratory test (in the absence of cholestatic liver damage, which can also lead to the accumulation of copper) is the measurement of the copper content in the liver biopsy. In untreated patients, this parameter should be above 200 μg per 1 g of dry weight. Normally, this figure does not exceed 50 μg per 1 g of dry weight.

The measurement of daily excretion of copper in urine is a simple test that usually differentiates unaffected individuals from patients with hepatolenticular degeneration. Normally, the daily excretion of copper is 20-45 μg. In hepatolenticular degeneration, the daily excretion always exceeds 80 μg. The indicator of daily excretion of copper, exceeding 125 μg is an absolute diagnostic sign of the disease. If this index is in the range from 45 to 125 mcg, then the patient can be either heterozygous or homozygous for the gene of hepatolenticular degeneration. Measuring the excretion of copper in 2 days can improve the accuracy of the test.

The determination of the level of ceruloplasmin in serum is most often used to diagnose hepatolenticular degeneration. However, in 10% of cases the level of ceruloplasmin remains normal (> 20 mg / dL). But even in patients with a low level of cerulplasmine (<20 mg / dL), it can increase on a particular length of the disease due to liver disease, pregnancy, or estrogen administration. A decrease in the level of ceruloplasmin is possible in other diseases, for example, in conditions accompanied by loss of protein, copper deficiency, Menkes disease, fulminant hepatitis, as well as in persons heterozygous for hepatolenticular degeneration.

Thus, if neurological and mental symptoms make it possible to suspect a patient of hepatolenticular degeneration, it should be examined with a slit lamp. If, in doing so, the Kaiser-Fleischer rings are detected, then the diagnosis is virtually indisputable. The determination of the level of ceruloplasmin, the content of copper in the serum, the daily excretion of copper in the urine is carried out in order to confirm the diagnosis and obtain the initial guidelines for subsequent monitoring of treatment. MRI can provide important diagnostic information. If a patient develops neurological symptoms, he usually has a change in MRI. Although the hepatolenticular degeneration gene has been identified, in most family cases, its unique mutation is revealed, which makes it difficult to diagnose with molecular genetic research in clinical practice. However, with the development of modern technology, by improving the methods of molecular genetic research, this diagnostic method will become available.

With Wilson-Konovalov's disease, the levels of ceruloplasmin and copper in the serum are usually reduced. Differential diagnosis of Wilson-Konovalov's disease is carried out with acute and chronic hepatitis, in which the level of ceruloplasmin can be reduced due to a violation of its synthesis in the liver. Malnutrition also reduces the level of ceruloplasmin. When taking estrogens, oral contraceptives, with obstruction of the biliary tract, during pregnancy, the level of ceruloplasmin may increase.

Daily excretion of copper in Wilson's disease is increased. To avoid distortion of the results of the analysis, it is recommended to collect urine in special bottles with a wide neck with plastic bags-disposable liners, which do not contain copper.

If there are contraindications to liver biopsy and at a normal level of ceruloplasmin in the serum, the disease can be diagnosed by the degree of inclusion in the ceruloplasmin of orally taken radioactive copper.

1. General blood test: increased ESR.
2. Urinalysis: Proteinuria, aminoaciduria is possible, an increase in the excretion of copper is greater than 100 μg / sug (the norm is less than 70 μg / day).
3. Biochemical blood test: increase in the content of AlAT, bilirubin, alkaline phosphatase, y-globulin, ceruloplasmin-unrelated copper in serum (300 μg / l and more), decrease or absence of ceruloplasmin activity in blood serum (usually 0-200 mg / l with norm 350 ± 100 mg / l).

Instrumental data

1. Ultrasonic and radioisotope scanning of the liver: enlargement of the liver, spleen, diffuse changes.
2. Liver biopsy: a picture of chronic active hepatitis, liver cirrhosis, excessive copper content in liver tissue. Despite the uneven deposition of copper in the cirrhotic liver, it is necessary to determine its quantitative content in the biopsy. To do this, you can use a cloth filled in a paraffin block. Normally, the copper content is less than 55 μg per 1 g of dry weight, and for Wilson's disease it usually exceeds 250 μg per 1 g of dry mass. A high copper content in the liver can be detected even with a normal histological picture. With all forms of long-persistent cholestasis, a high copper content in the liver is also found.
3. Scanning. Computerized tomography of the skull, performed before the appearance of neurologic symptoms, can reveal an increase in the ventricles, as well as other changes. Magnetic resonance imaging is more sensitive. It can reveal the expansion of the third ventricle, the lesions in the thalamus, the shell and the pallid sphere. These lesions usually correspond to clinical manifestations of the disease.

Identification of homozygotes with asymptomatic course of Wilson-Konovalov's disease

Brothers and sisters of the patient should be examined. The homozygosity is evidenced by hepatomegaly, splenomegaly, vascular sprouts, a slight increase in the activity of transaminases in the serum. The Kaiser-Fleischer ring is not always revealed. The level of ceruloplasmin in the serum is usually reduced to 0.20 g / l or less. A liver biopsy with a determination of the copper content allows you to confirm the diagnosis.

It is easy to distinguish homozygotes from heterozygotes, although difficulties may sometimes arise. In such cases, the haplotypes of the patient and his brothers and sisters are analyzed. Homozygotes are treated with penicillamine, even if the disease is asymptomatic. Heterozygotes do not need treatment. When observing 39 clinically healthy homozygotes receiving treatment, no symptoms appeared, while 7 untreated homozygotes developed Wilson's disease and 5 of them died.