Menkes trichopolydystrophy

Menkes trichopolydystrophy (kinky hair disease, OMIM 309400) was first described by JH Menkes in 1962. The incidence of the disease is 1:114,000-1:250,000 newborns. It is inherited recessively linked to the X chromosome. The gene is localized on chromosome Xql3.3. As a result of a gene mutation, a deficiency of ATPase, which carries out transmembrane transfer of cations, develops. It is believed that the function of this protein is to transfer copper from the cell to the extracellular environment. Disruption of the metabolism of this element and its transport leads to a deficiency of copper-containing enzymes: lysyl oxidase, cytochrome oxidase, tyrosinase, monoamine oxidase, axorbic acid oxidase, superoxide dismutase, dopamine beta-hydroxylase, as well as to a decrease in ceruloplasmin in the blood. Pathogenesis is associated with decreased copper absorption in the intestine, low levels in the blood, liver cells, brain, but an increase in its amount in the intestinal mucosa, spleen, kidneys, muscles, lymphocytes, fibroblasts. Excess copper is associated with the effect of the metallothionene protein, which is present in large quantities in cells. Deficiency of many enzymes leads to the development of various disorders:

• disruption of the synthesis of collagen and elastin fibers;
• disruption of the structure of the inner surface of blood vessels;
• disruption of bone tissue mineralization processes;
• increased fragility, curling and depigmentation of hair;
• tissue respiration disorders;
• an increase in L-DOPA in the blood and cerebrospinal fluid, and disorders of neurotransmitter metabolism.

Some authors suggest that the defect in this disease concerns the zinc-bound protein that induces the synthesis of metallothionene, and the disturbance of copper metabolism is secondary.

Menkes disease is a genetically heterogeneous disease.

Symptoms of Menkes trichopolydystrophy. Almost half of patients with Menkes syndrome were born prematurely. The manifestation of the disease in most cases is early - from the first days of life. Hypothermia develops, the child refuses to eat, gains weight poorly. Subsequently, convulsions, myoclonus of the muscles of the face, limbs, resistant to anticonvulsant treatment join in. The child loses the ability to hold the head, muscle tone decreases, which is replaced by dystonia and spastic paresis. A sharp lag in neuropsychic development is observed. A characteristic sign is altered hair - sparse, hard, brittle and twisted (pilli torti). The skin also suffers - increased extensibility, dryness, pallor. The child sometimes takes the form of a "cherub" - hypomimic, with a low position of the bridge of the nose. Vision is reduced due to partial atrophy of the optic nerves. Microcysts of the retina may be detected in the fundus. Changes in the skeletal system may manifest themselves as repeated fractures of the extremities. Disorders of the genitourinary system: nephrolithiasis, malformations (diverticulum of the bladder, hydronephrosis, hydroureter). In some patients, microanomalies are detected (micrognathia, high palate).

The disease is progressive. Patients usually die in the 1st to 3rd year of life from septic complications or subdural hemorrhages.

In atypical forms, the disease manifests itself late, but is milder and the life expectancy of patients is 13.5 years.

Menkes syndrome has been described in women, but in these cases it is usually associated with Shereshevsky-Turner syndrome. Women who carry the Menkes syndrome gene often have no signs of the disease, but 40% of them have coarse, curled hair.

EEG data reveals multifocal paroxysmal changes or hypsarrhythmia.

CT or MRI results reveal atrophy of brain and cerebellar tissue, decreased density of white matter areas of the brain, the presence of subdural hematomas, widening of the Sylvian fissure, and pachygyria.

X-ray examination of tubular bones reveals thickening of the cortical layer, changes in the metaphyseal zones, and a diphyseal periosteal reaction.

Hair microscopy: twisting along the longitudinal axis (pilli torti), change in caliber (monilethrix), increased fragility (trichorrhexis nodosa).

Morphological examination of the brain reveals areas of gray matter degeneration with loss of neurons and gliosis, especially in the cerebellum. Electron microscopy reveals an increase in the number of mitochondria, a change in their size, and electron-dense bodies inside them. In the white matter, there is axonal degeneration. In the skin and inner lining of blood vessels, there is fragmentation of elastic fibers.

In muscle tissue, the activity of mitochondrial enzymes of complexes 1 and 4 of the respiratory chain is reduced.