Basics of Medical Genetics - Buzhiyevska T.I. 2001

Hereditary diseases
Disorders of metal metabolism

The best-known pathology in this group is hepatolenticular degeneration (Wilson's disease). This condition typically manifests between the ages of 12 and 20. Affected individuals experience weakness, abdominal pain, jaundice, tremor, muscular rigidity, hyperkinesia, dysphagia, dysarthria, and pseudobulbar symptoms. A characteristic greenish-brown ring (the Kayser—Fleischer ring) appears along the outer edge of the cornea. The disease presents in several forms: abdominal, early rigid-arrhythmic-hyperkinetic, tremor-rigid, and extrapyramidal-cortical. The abdominal form is frequently misdiagnosed as Viral Hepatitis progressing to Liver cirrhosis. Hepatolenticular degeneration is accompanied by dementia and is inherited in an autosomal recessive (AR) manner. It is caused by a mutation in a Gene located on chromosome 13, which is involved in copper METABOLISM. This defect leads to copper accumulation in the Blood and the deposition of this metal in the Cells of the liver, Brain, Kidneys, Spleen, iris, cornea, and lens of the eye.

The ceruloplasmin protein (encoded by a gene on chromosome 6), the defect of which was previously considered central to the Pathogenesis of Wilson's disease, is now recognized as playing a primary role in iron metabolism disorders (Fe₂—>Fe₃) as well as The Development of anemia and hemosiderosis. Treatment protocols involve detoxification therapy (such as unithiol and hemodez), penicillamine, kuprbnil, or other chelating agents, alongside zinc oxide and sodium tetraborate. Dietary restrictions are essential: copper-rich foods (brain, liver, nuts, dried fruits, etc.) must be eliminated, and cooking in copper utensils is strictly prohibited. B-complex Vitamins, choleretic agents, and copper-containing medications are contraindicated. With proper and consistent long-term management, the clinical picture improves significantly.

Another severe condition caused by a genetic defect in copper metabolism is Menkes syndrome, which manifests in the neonatal period with intractable seizures, thermoregulation disorders, jaundice, feeding refusal, and lethargy. Visual acuity declines rapidly. The Hair becomes extremely kinky, brittle, and hypopigmented, accompanied by symptoms of Osteogenesis Imperfecta. The underlying pathology stems from impaired intestinal absorption and transport of copper, a process dependent on the copper-containing enzyme cytochrome c oxidase. Copper levels are decreased in The Liver and ceruloplasmin levels are reduced in the blood serum. Menkes syndrome is inherited in an X-linked recessive (XR) manner. Treatment involves the parenteral administration of copper salts and copper-Histidine complexes—ideally during the antenatal period to prevent irreversible brain and bone damage. In the postnatal phase, copper salts are administered intravenously under strict monitoring of serum copper levels.