The genetic mirror image Wilson Vs Menkes

Описание: Menkes disease, also known as kinky hair syndrome, is a rare X-linked recessive condition caused by pathogenic variants in the ATP7A gene. This gene encodes a copper-transporting ATPase responsible for delivering copper to cuproenzymes and facilitating copper export from enterocytes. Characteristic features include light-colored, sparse, and brittle hair; thin or absent eyebrows; high-arched palate; full cheeks; and hyperelastic, doughy skin. Neurologic manifestations such as hypotonia and seizures typically emerge within the first few months of life. The condition predominantly affects males, and early recognition is essential for timely diagnostic testing and consideration of copper-histidine therapy.

Menkes disease results from ATP7A mutations, not ATP7B. Although both genes encode copper-transporting ATPases, their tissue expression patterns and pathophysiological effects differ. ATP7A is expressed in most tissues except the liver and is essential for copper uptake and systemic distribution. In contrast, ATP7B is expressed primarily in hepatocytes and mediates copper excretion into bile. Defects in the ATP7B gene lead to Wilson disease, an autosomal recessive condition characterized by copper overload. This distinction is clinically important for understanding copper disorders with opposing biochemical profiles—Menkes causes deficiency, and Wilson causes toxicity.

In Menkes disease, defective ATP7A impairs the absorption of dietary copper from intestinal epithelial cells into the bloodstream. This leads to systemic copper deficiency, which disrupts the function of several copper-dependent enzymes, including cytochrome c oxidase, lysyl oxidase, and dopamine beta-hydroxylase. These deficiencies explain the multisystem manifestations of the disease, such as connective tissue weakness, vascular fragility, neurologic decline, and abnormal hair structure. Copper accumulates in enterocytes and other tissues where ATP7A is active, but fails to reach target enzymes, resulting in functional deficiency despite localized excess.

ATP7B mutations lead to Wilson disease, an autosomal recessive disorder of copper accumulation that presents later in life with hepatic and neuropsychiatric symptoms. It does not cause brittle hair, hypotonia, or subdural hematomas. Disorders of pyruvate metabolism may cause neonatal seizures and encephalopathy but do not involve connective tissue or copper transport defects. Although many metabolic conditions with severe neonatal presentations are autosomal recessive, this patient's disorder is not. Menkes disease is caused by mutations in the ATP7A gene, which is located on the X chromosome. Its inheritance is X-linked recessive.