Menkes disease (curly hair disease) is a rare genetic disease in which copper metabolism is disrupted in the body. Pathology has an X-linked recessive type of inheritance. Menkes disease is manifested by a lag in mental and physical development, brittle curly hair, cerebral neurodegenerative lesions. Diagnosis of the disease involves genetic analysis, the study of the concentration of copper, ceruloplasmin, neuroimaging methods (magnetic resonance imaging and computed tomography of the brain). In case of curly hair disease, replacement therapy with parenteral copper preparations, symptomatic treatment with anticonvulsants and analgesics is carried out.
ICD 10
E83.0 Copper metabolism disorders
General information
Pathology refers to orphan diseases, occurs with a frequency of 1:40,000 to 1:250,000 newborns. The disease develops only in boys and is named after the pediatric neurologist J. H. Menkes, who described the characteristic symptoms in 1962. An easy variant of the pathology is occipital horn syndrome, which manifests after one year of age and does not cause fatal complications. Its distinctive features are excessive calcification of the occipital bone, coarse and coarse hair, flabbiness of the skin.
Causes
The etiological factor of pathology has been deciphered thanks to the achievements of medical genetics. Menkes disease occurs when the polypeptide alpha ATP7A gene mutates, which regulates the ATPase responsible for the transport of copper ions. The change occurs on the long arm of the X chromosome at the Xq12-q13 locus. Curly hair disease has recessive inheritance, so it affects only boys. The girls are carriers of the mutant gene, but no cases of their disease have been recorded.
Pathogenesis
With this hereditary pathology, the structure of one of the transmembrane proteins is disrupted, as a result of which copper ions cannot be transported normally and participate in metabolic processes. The child has a deficiency of copper-containing proteins, which are normally used for metabolism, tissue respiration, redox reactions.
The lack of trace element causes violations of melanin production, a decrease in the concentration of collagen and keratin in tissues, a decrease in the ability to detoxify free radicals. An important link in the pathogenesis is a decrease in dopamine synthesis, which provokes serious neurological disorders at an early age. Since the copper-containing protein ceruloplasmin is responsible for the oxidation of iron, in its absence, hematopoiesis is inhibited.
Symptoms
Menkes disease can cause pregnancy complications — difficult or premature birth, but up to 70% of women do not face pathologies of the intranatal period. Some infants have cephalomatomas and fractures during childbirth, even in the absence of active actions by obstetricians. Alarming symptoms include funnel-shaped deformity of the chest, congenital umbilical or inguinal hernia.
The first signs of curly hair disease appear during the newborn period. The baby has hypothermia, prolonged jaundice with high bilirubinemia, and the terms of physiological postpartum adaptation are lengthened. Sometimes in the neonatal period, parents notice characteristic hair changes: the formation of nodules and the formation of fusiform (“curly”) hairs. At this time, the physical and mental development of the newborn corresponds to the norm.
Obvious signs of a genetic disease are registered after 2-3 months of life. A neurological deficit becomes noticeable. The child lags behind in psychomotor development and forgets previously acquired skills, he has periodic convulsive seizures. In the later stages, the disease is manifested by spastic tetraparesis due to extensive neurodegenerative cerebral processes. The skin acquires a painful pallor and a yellow tint.
In the first year of life, pathognomonic changes in the form of curly hair are detected due to trichopolydystrophy, thanks to which the genetic syndrome received a second name. The hair becomes dull and stiff, acquires a gray or “gray” shade, twists into tight spirals. Disorders of collagen metabolism are manifested by excessive skin extensibility and hyper-mobility in the joints, which clinically resembles Ehlers-Danlos syndrome.
Complications
For curly hair syndrome, anomalies of the urinary system are typical, especially diverticula of the urinary tract, which cause recurrent urogenital infections. Vascular anomalies are widespread — elongation, excessive tortuosity and changes in the diameter of the arteries. The vessels of the brain and skin are most often affected. Children develop generalized osteoporosis and spontaneous fractures. Menkes disease is associated with seborrheic dermatitis.
The late consequences of the disease include blindness, respiratory failure. Cardiovascular complications are the most severe. The child may have thrombotic disorders, spontaneous ruptures of arteries, hematomas. Most patients die in the first 3 years of life from generalized infections, intracranial hemorrhages, gross neurodegenerative processes.
Diagnostics
An experienced pediatrician may assume curly hair disease during a physical examination of the child, identification of characteristic trichopolydystrophy and neurological disorders. Diagnosis involves instrumental visualization to assess the condition of the affected organs and laboratory tests to verify copper metabolism disorders and gene mutations. The main components of the diagnostic plan:
- MRI of the brain. Neuroimaging studies show foci of cortical and subcortical atrophy, focal areas of gray matter necrosis. A typical symptom of Menkes disease is cerebellar atrophy. If an intracranial hemorrhage is suspected, a CT scan of the brain provides high information.
- EEG. The study is carried out to find out the cause of seizures and to detect foci of epileptiform activity in the brain. According to the electroencephalogram, the neurologist diagnoses slow-wave activity and the presence of multifocal adhesions.
- Blood test. A study of the level of ceruloplasmin provides valuable information for diagnosis. In Menkes syndrome, as well as Wilson-Konovalov disease, this indicator is reduced. To clarify the diagnosis, a biochemical examination of liver biopsies is performed and a decrease in copper content is detected.
- Genetic tests. To confirm the mutation, medical and genetic counseling of the child and his parents is recommended. To identify the pathology of the ATP7A gene, the genetic code and DNA sequence disorders in the corresponding section of the boy’s X chromosome are determined. According to the indications, the examination of the child’s mother is carried out.
Treatment
Effective treatment has not yet been developed. To reduce the deficiency of trace elements and improve metabolism, copper is administered parenterally in the form of histidinate. This method of obtaining the mineral guarantees its delivery to all organs and tissues, which activates enzyme systems, normalizes oxidative phosphorylation and the work of the nervous system.
The results of clinical studies show that early administration of copper in parenteral forms slows down the progression of neurological deficiency and prolongs the life of children with curly hair disease. In them, the disease proceeds in a milder form, without seizures and severe cognitive impairment. The complexity of treatment lies in the timely diagnosis of pathology, which is associated with its rare occurrence.
Symptomatic therapy includes analgesics, anticonvulsants and psychotropic drugs. They are designed to make the patient’s life easier. If natural feeding is impossible, a probe is inserted or parenteral nutrition is used. A child who has been diagnosed with Menkes disease requires comprehensive rehabilitation with the participation of physiotherapists, psychologists, speech therapists.
Prognosis and prevention
Given the inability to influence the genetic mechanisms of pathology and the absence of etiotropic treatment, the prognosis is unfavorable. Most children suffering from curly hair disease do not live more than 3 years. Modern rehabilitation methods help to improve their quality of life and help parents in caring for a special baby. Prevention of Menkes syndrome includes genetic counseling for couples with a burdened family history.