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"Child`s Health" 8 (59) 2014

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Clinical case of disease Wilson - Konovalova (Hepatolenticular degeneration) of a child

Authors: Tsytsyura O.O., Lembryk I.S., Tymoshchuk O.V., Shlimkevych I.V., Turkin Yu.V., Kutsela I.A. - High State Educational Institution "Ivano-Frankivsk National Medical University"; Department of Pediatrics (Head. Department. Prof. Volosyanko A. B.); Regional Clinical Hospital (Chap. Physician Koturbash R.Y.)

Categories: Pediatrics/Neonatology

Sections: Specialist manual

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children, disease, hepatitis, cirrhosis, treatment.

Introduction. The above observation demonstrates the clinical picture of Wilson disease and aims to draw attention to the possibility of early diagnosis of this pathology [ ]. In practice of children gastroenterologist there are numerous cases of diseases that run across unusual, with clinical "masks" of other organs and systems, and it is often difficult to diagnose the underlying disease, degrades the quality of life of the sick child [ ].

Definition. Wilson's disease - an inherited (autosomal recessive) disease, which is based on a genetic defect of copper metabolism that results in excessive accumulation of this element in the body and toxic damage caught up in the process of organs and tissues, mainly the liver and brain [].

Prevalence of Wilson's disease is an average from 1 to 30 000 in Japan, from 1 to 100 000 in Australia []. The frequency of heterozygous carriers - 1:90. In today's world, there are from 10 to 30 million patients

and the frequency of gene detection ranges 0.3-0.7%  [].

Wilson's disease - caused by an inherited defect of one of transforming copper-ATPase []. The disease is a defect in the gene ATF7V, which is localized to chromosome 13 (13q14.3-q21.1) and encodes a copper-transporting protein adenozyntryphosphataz (ATPase) P-type responsible for intracellular transport of copper ions.

Currently, more than 300 described mutations that may explain clinical polymorphism disease []. The pathogenesis of the disease is insufficiently studied. The gene encodes ATRV enzyme that carries copper excretion into bile and copper from ceruloplasmin []. The excretion of  copper from the liver into bile in this disease is reduced to 20-30% of normal, respectively, and reduced copper excretion with stool [].

It is assumed that the patient is not able to produce enough ceruloplasmin - blood protein that binds copper and is involved in its transportation. It is known that 95% of copper in serum ceruloplasmin is in stock. Ceruloplasmin plays an important role in the metabolism of iron. According to another hypothesis first chain disease is copper metabolism in the liver and reduces ceruloplasmin - its consequence. No matter who is the first chain, copper accumulates in the liver, leading to toxic effects of damage to the mitochondria and hepatocytes peroxide. The postponement of copper in the brain causes the development of coarse neurological symptoms, and the iris - the formation of ring-Kaiser Flashner (accumulation of brown-green pigment).

The case presented by us, will be interesting to pediatricians and other doctors (gastroenterologists, neurologists, geneticists, psychiatrists) due to the severity of disease diagnosis. It is interesting medical history of the child B., age 10 of Wilson's disease and cirrhosis of the liver.

Patient B., 10 years old, hospitalized in the gastroenterology department of Ivano-Frankivsk Regional Pediatric Hospital with complaints of fever to 380, pain and swelling of the lower extremities, increasing the stomach, the yellow color of the skin and sclera, rash on the face, decreased appetite, aggression, lethargy .

First child was hospitalized in regional clinical infectious hospital where acute hepatitis were excluded.

From history: child of 1st full-term pregnancy, which occurs with toxicity and the threat of termination. Genera timely, weight – 3400gr, ut to 3 months was breastfed. Growth and development corresponds to the age. The child is three years old, was operated on testicular hydrocele, inguinal hernia. The family has two younger sisters. Closely marriages are not registered in the pedigree. In the study of clinical and family history, it was found that the patient's uncle on the father logoneurosis of 6 years and 20 years - hand tremor.

At 8 years old,  mother noticed complaints that the boy was distracted, irritable, started worse in school, lost interest in learning, impaired memory, there was a "slight" yellowing sclera.

At admission to the hospital the child's condition was difficult due to intoxication syndrome. On examination correct body structure, a moderate recovery, weight 35 kg. Abdomen increased in size, abdominal circumference 66cm. From mouth  is felt typical "liver" smell. Skin and visible mucous membranes are pale yellow,  sclera is yellow, the skin of the forehead - multiple elements Acne vulgaris, the skin of the chest and arms - vascular "stars", expressed "marble" of the  limbs. The boundaries of the heart within age norms, cardiac sonorous, rhythmic, systolic murmur more expressed at Botkin, conducted under the shoulder blade. Percussion - dulling of the lungs sound at the bottom right of fate. Abdominal palpation soft and painless. Positive symptom of "fluctuations". Liver – up to + 3 cm below the costal arch, rounded edge, spleen - circle the costal arch and soft. Edema of the lower extremities. Vesicles negative symptoms. Muscle tone is slightly elevated. At question is answered slowly, composite.

An examination of the patient:

Complete blood analysis: Hb -109h / l, Er 3.95 * 1012 / L, LC-6.4 * 109 / L, E-6% P-3% S-52% A-32% M-7%, Tr-131 * 109 / L, SHOE-7mm / h.

Urinalysis: pH 6.5, specific gravity, 1020, Ep.-vp.z. 1-2, 3-5 in LC-, entitled,-oxalate salt sparingly urobilin-1 mg / dL, ketone bodies -10mh / dl.

Proteyinogramma: common  protein - 56,4h / l, albumin, 42.1%, alpha 1 - 6.1% alfa2-8,9%, 14.2% beta-, gamma-28.6% A / d- 0.72.

Immunogramma: IgG-12,5h / l, IgA-2.0 g / l, IgM-4.3 g / l, CIC-0,034h / l.

Coagulogramma: PTI-54%-refraction bunch more 180s, fibrinogen ++ ah.fibrynohen-1.8.

Biochemical blood test: common. bilirubin 68.0 mmol / l, direct - 28.0 mmol / l, indirect - 40 mmol / L, ALT 90 mmol / L, AST - 150 mg / dL, thymol test - 6od, urea-3,96mmol / l, creatinine-0,059mkmol / l sugar 5,85mmol / l, cholesterol -4,47mmol / l.

Re-examination of serum for anti-HAV IgM, HBsAg and anti-HCV, and HGV RNA gave negative results. Due to the fact that markers of viral hepatitis have been detected child studied serum ceruloplasmin in the blood.

Serum ceruloplasmin - 89,6mh / l (normal 200-600mh / l) - reduced.

The excretion of copper in urine - 0,32mh / l (normal 0,012-0,08mh / l), 0.64 mmol / L (normal 0,018-0,12mkmol / l).

Ultrasound of abdominal cavity organs: liver - the size is not enlarged, the edge sharp, thickened capsule to 1mm, diffusely heterogeneous parenchyma, small hyperechoic nodes 3-7mm diameter, portal vein diameter - 10 mm, the rate of blood flow in the portal vein increased to 33cm / s.

MRT of the brain: characteristics of symmetrical lesions of subcortical nuclei, bridge and legs midbrain (like a spongy degeneration), violation of foreign and domestic liquor dynamics of the open type.

Consultation with an ophthalmologist: pathology and corneal crystals were not found during the inspection of the fundus - narrow retinal vessels (arterioles S <D), venous plethora No available Kayser-Flascher rings, which represent a golden or brownish-green ring around the iris of the eye.

Consultation with a psychiatrist: astheno-hypochondriac syndrome. Hysteria. The effects of organic brain damage and somatic disease in the form of mild cognitive failure and emotional lability.

Needle biopsy of the liver in order to quantification of hepatic copper concentration was not carried out because of the disastrous state of the patient.

Molecular genetic studies confirmed the diagnosis of Wilson's disease. A study was conducted DNA sample for the presence of frequent mutations in exons 14 and 15 gene ATR7V. In exon 14 was found frequent mutation (S3207A), the second - unidentified.

Differential diagnosis was conducted between infectious hepatitis, immune hemolytic anemia and hereditary hemolytic anemia. Examination of quantitative and qualitative composition of Hp, osmotic resistance of erythrocytes and antioxidant status abnormalities not demonstrated that allowed to exclude hemolytic anemia associated with erythrocyte membrane disorders and hereditary hemoglobinopathia. Conduct twice Coombs test gave a negative result.

Performance of complex laboratory tests (reduction of ceruloplasmin, increased urinary copper excretion, negative markers for hepatitis)  presence of Kaiser-Fleshner rings during the examination by ophthalmologist were allowed to expose diagnosis of disease Wilson-Kivalova, hepatic form. Cirrhosis, Class B by Child Pyu.

Portal hypertension, compensated form. Astheno-hypochondriac syndrome. Hysteria. The effects of organic brain damage and somatic disease in the form of mild cognitive failure and emotional lability.

The patient was prescribed a diet with the exception of products containing copper and drug Cuprenil (D-penicillamin) at a dose of 500 mg / day. To remove toxicity and improve liver function were prescribed vitamin B6, Dufalak, Heptral, Troxevasin, Cardona, Veroshpiron, Ursofalk. Against the background of therapy the patient's condition gradually improved.


Thus, Wilson's disease is characterized by multisystem nature of the lesions, progressive course. It is necessary to take into account, in addition to gastrointestinal symptoms, neurological symptoms, mental disorders of behavior and cognitive functions. Relatives of patients with Wilson's disease should examine, even if no clinical symptoms.

Prospects for further research. The study of clinical features and other manifestations of Wilson's disease in order to improve diagnosis of this disease.

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