Trigopolydystrophy of Menkes

Menkes' trichopolydystrophy (curly hair, OMIM 309400) was first described by JH Menkes in 1962. The incidence 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. Due to mutation of the gene, there is a deficiency of ATPase, which carries out the transmembrane transfer of cations. It is believed that the function of this protein is to transfer copper from the cell to the extracellular environment. The disruption of the exchange of this element and its transport leads to a deficiency of copper-containing enzymes: lysyloxidase, cytochrome oxidase, tyrosinase, monoamine oxidase, oxidoric acid, superoxide dismutase, dopamine beta-hydroxylase, and a decrease in the blood of ceruloplasmin. Pathogenesis is associated with a decrease in copper absorption in the intestine, a low level in the blood, cells of the liver, the brain, but an increase in its quantity in the intestinal mucosa, spleen, kidneys, muscles, lymphocytes, fibroblasts. Excess of copper is associated with the effect of the metallothionen protein, which is present in large quantities in cells. Deficiency of many enzymes leads to the development of a variety of disorders:

• the synthesis of collagen and elastin fibers;
• violation of the internal structure of the vessels;
• violation of the processes of mineralization of bone tissue;
• increased brittleness, twisting of hair and their depigmentation;
• disorders of tissue respiration;
• increase in blood and cerebrospinal fluid L-Dopa, neurotransmitter metabolism disorders.

Some authors suggest that the defect in this disease concerns a zinc-linked protein inducing the synthesis of metallothionen, and the violation of copper exchange is secondary.

Menkes disease is a genetically heterogeneous disease.

Symptoms of Trichopolidystrophy Menkes. Almost half of the patients with Menkes syndrome were born prematurely. The manifestation of the disease in most cases is early - from the first days of life. Developing hypothermia, the child refuses to eat, poorly increases weight. Later, convulsions, myoclonias of the muscles of the face, limbs, resistant to anticonvulsant treatment are added. The child loses the ability to hold his head, lowering the muscle tone, which is replaced by dystonia and spastic paresis. Observe a sharp lag in the neuropsychological development. A characteristic feature - changed hair - rare, stiff, brittle and twisted (pilli torti). Also affects the skin - increased stretch, dryness, pallor. The child sometimes takes the form of a "cherub" - hypomimous, with a low location of the bridge of the nose. Vision is reduced due to partial atrophy of the optic nerves. On the fundus, microcysts of the retina can be detected. Changes in the osseous system can be manifested by repeated fractures of the limbs. Disorders of the genitourinary system: nephrolithiasis, malformations (bladder diverticulum, hydronephrosis, hydroureter). A number of patients have microanomalies (micrognathia, high palate).

The disease has a progressive nature. Patients usually die in the 1-3th year of life from septic complications or subdural hemorrhages.

Atypical forms of the disease manifest late, but it is easier and the life expectancy of patients is 13.5 years.

The occurrence of Menkes disease in women is described, but, as a rule, in these cases it was combined with the Shereshevsky-Turner syndrome. The bearers of the gene of the Menkes syndrome often have no signs of disease, but 40% of them observe stiff curled hair.

According to EEG findings, multifocal paroxysmal changes or gypsarhythmia are identified.

According to the results of CT or MRI, atrophy of the brain and cerebellum tissue is detected, a decrease in the density of white matter areas of the brain, the presence of subdural hematomas, expansion of the sylvium furrow, and pachygyrium.

Radiologic examination of the tubular bones reveals a thickening of the cortical layer, a change in the metaphyseal zones, and a dysthymic periosteal reaction.

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

Morphological examination of the brain reveals the causes of degeneration of gray matter with the 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 white matter, degeneration of axons. In the skin and inner shell of the vessels - the fragmentation of elastic fibers.

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