Mucopolysaccharidosis - a set of genetically determined pathologies having a common pathogenetic mechanisms of development is incomplete destruction and accumulation of mucopolysaccharides.The clinical picture mucopolysaccharidosis formed depending on the structure of the lesion, which accumulated excessive amounts of glycosaminoglycans.The most common mucopolysaccharidosis in children and is a scientifically proven fact transmit the abnormal gene is inherited.
This pathology is extremely rare, but the researchers' attention focused on the problem of finding an effective method to treat it, as the mortality rate is very high from mucopolysaccharidosis.
All forms and types of MPS are classified as hereditary diseases transmitted autosomal recessive mode of inheritance.Mutation is a change in the gene structure of a gene lysosomal alpha irunidazy, which is directly involved in the metabolic conversion of glycosaminoglycans.As a result
defeat lysosomal alpha irunidazy, is a violation of vnutrilizosomnogo decay and excess dermatan its accumulation in the hepatic and splenic parenchyma, cartilage and periosteum, nerve tissue, and the vascular wall.
a result of the progression of mild swelling of the meninges develops partial occlusion of the subarachnoid space, in turn, contributes to the progression of hydrocephalus.The cause of the child's symptoms of mental retardation is excessive accumulation of ganglioside in neurons.
addition pronounced metabolic disorders mucopolysaccharides showing signs of metabolic disorders of proteins, which are manifested in the form of giperaminoatsidurii.
Symptoms of Mucopolysaccharidosis
All patients with mucopolysaccharidosis have a specific distinctive phenotypic traits in the form of ugly facial features with extended tongue and a big head.Patients with any type of mucopolysaccharidosis have signs fizikometricheskom backlog in development, namely, disparity passport bone age, the development of a pronounced degree of scoliosis and disfiguring contractures of large joints.
Despite the predominantly damage to the nervous and / or musculoskeletal system, for certain types of mucopolysaccharidosis observed damage to internal organs.
distinctive characteristic symptoms mucopolysaccharidosis deemed to be affected neurons of cortical structures of the brain, so that the child develops signs of intellectual abilities of varying degrees of intensity.When the progressive course of the disease is almost 100% of mucopolysaccharidosis celebrated defeat of the optic nerve and cornea of one / both eyes, accompanied by a marked disturbance of visual function.
♦ The most severe form of this disease is considered mucopolysaccharidosis type 1, accompanied by a profound impairment of neurological status of the child and a comprehensive defeat of almost all vital organs and systems.
debut of disease falls on the chest and is accompanied by a period of severe violations of the shape and size of the cranium, kifoskolioticheskoy deformation of the spine and small joints contractures.In this category of patients have congenital enlarged liver and muscle weakness, tendon inguinal ring with the emergence of signs of inguinal hernias.
In the early stages of the disease diagnosis "mucopolysaccharidosis" rarely established due to the fact that this pathology is classified as rare.However, the progression of disorders of physical and mental development of the child in conjunction with external displays allows to put mucopolysaccharidosis type 1 in the differential diagnoses.
neurological status of the child suffering from mucopolysaccharidosis type 1, has the characteristic features in the form of signs of hypertensive-hydrocephalic symptom, namely the increase in the size of brain of the skull, the emergence of enlarged venous network in the temporal areas, and autonomic dysfunction.When the X-ray of the skull in lateral projection noteworthy slight increase in the size of the sagittal sella, and lumbar puncture to determine elevated cerebrospinal fluid pressure.The pathogenesis of neurological disorders in patients with mucopolysaccharidosis type 1 based on changes in bone structure of the skull and in the projection of increased hydrophilic component of the connective tissue of the brain tissue.
defeat of the internal organs in mucopolysaccharidosis type 1 occurs in the long term lies in the formation of valvular defects, corneal opacities.Due to the fact that this pathology is accompanied by severe disorders of brain structures, it belongs to the category of adverse against the child's life, the duration of which does not exceed a ten-year milestone.Laboratory chromatographic urine of children suffering from this type of mucopolysaccharidosis, accompanied by the definition of high-level indicators glucosamine abroad exceeding 300 mg per day.
♦ Mucopolysaccharidosis type 2 is similar to the previous form of clinical manifestations, but it is a characteristic feature of the predominant involvement of males in the first year of life.The phenotypic manifestations of this pathology are less pronounced compared with mucopolysaccharidosis type 1, but emphasize the genetic origin of the disease: growth retardation, hypertelorism and flattened nose, shortening of the cervical spine and the large size of the language.
main feature of mucopolysaccharidosis type 2 is a complete absence of evidence of the static deformation of the spine in the form of kyphoscoliosis.Infringement of intellectual-mental functions of the cerebral cortex has a smaller display, but in most cases, the children formed sensorimotor signs of hearing loss.Eye involvement is in only small changes in the stagnant bilateral optic nerve and turbidity of the surface layers of the cornea.
for mucopolysaccharidosis type 2 is characterized by the manifestation of the endocrine and autonomic-trophic changes in the form of abdominal type of obesity, hypertrichosis and acrocyanosis.Children suffering from mucopolysaccharidosis type 2 belong to the category of risk of occurrence of respiratory viral diseases, complicated by bacterial pneumonia.Diagnostic criterion mucopolysaccharidosis diagnosis in this situation is to increase the performance of chromatographic heparan sulfate or dermatan sulfate in urine.
♦ Sanifilippo syndrome, or mucopolysaccharidosis type 3 equally affects children of both sexes and is accompanied by the development of a specific phenotypic appearance.Children suffering from mucopolysaccharidosis type 3 have malformations of brain and facial parts of the skull in the form of increased formation of the frontal bones, flattened nose, big lips and thick tongue, and closely spaced eye sockets.The defeat of the osteoarticular apparatus increasingly affecting the small joints than the spine, and is manifested in the form of congenital contractures of the interphalangeal and metatarsophalangeal joints of the hands and feet.Also for this congenital syndrome is not characteristic lesion of internal organs, but suffers from the neurological status of the child to a large degree.
From an early age children have a tendency to increased irritability and emotional instability, impaired memory and progressive braking intellectual activity.The diagnosis is usually set at a late stage of the disease by soliciting laboratory and instrumental methods of examination (rentgenomorfometriya, chromatographic determination of acid mucopolysaccharides, characterized by high levels of heparan sulfate).
♦ 4 type of mucopolysaccharidosis, or Morquio Syndrome is different from previous forms of favorable course, as this is not accompanied by gross pathology neurological defects and to a greater extent affect the development of bones and joints of the child.Children with Morquio syndrome have abnormal development of large rough tubular and flat bones, as well as the deformation of joints with severe violation of their functions.Laboratory examination of urine child suffering from mucopolysaccharidosis type 4, followed by the detection of increased content of dermatan.
♦ Sheye syndrome, or mucopolysaccharidosis type 5, a clinical and laboratory symptoms similar to the first type, but in this pathology observed a more aggressive course of the disease with a complete absence of periods of remission.In connection with this syndrome Sheye occupies a leading position in the structure of infant mortality mucopolysaccharidosis.The fundamental difference of this syndrome is the predominant involvement of the cardiovascular system to the formation of gross malformations valvular and large vessels.
♦ Children diagnosed with mucopolysaccharidosis type 6 may be a long time to live with the disease, because this pathology is not accompanied by a violation of intellectual-mental functions of the brain, and appears only in some corneal opacity having unilateral or bilateral character.Chromatographic urine, which is included in the algorithm of examination of patients with suspected mucopolysaccharidosis, to determine elevated levels in the absence of heparan sulfate with.
Treatment of mucopolysaccharidosis
important in the treatment of a child with MPS is early diagnosis with the definition of clinical and laboratory-type of this disease, as each variant of the disease requires an individual approach to the use of appropriate treatment.In determining the tactics of management and treatment of a patient suffering from mucopolysaccharidosis one type or another participating team of specialists, including a pediatrician-neonatologist, specialist plastic surgery, orthopedics, neurosurgery, ophthalmology and ENT.
As a rule, the treatment of mucopolysaccharidosis was to eliminate those or other signs of the disease, that is used symptomatic treatment option.The only pathogenetically substantiated treatment is currently considered a hormone, which allows not only to arrest the clinical manifestations, but also to neutralize laboratory manifestations of the disease.The optimal combination, can significantly reduce the activity of the synthesis of glycosaminoglycans by fibroblasts, it is a combination of thyroidin and prednisone (daily dosage of not less than 1 mg per 1 kg of weight of the child 2 months course).
It is also appropriate prescriptions, improves the function of fibroblasts, which include methionine at a daily dose of 0.75 mg orally.
Mucopolysaccharidosis type 1 is an absolute indication for bone marrow transplantation, in the absence of contraindications, and more efficient, this method has in the age of the patient up to two years.Available extraneural violation of the child are the justification for the use of replacement therapy using Aldurazima at a dosage of 100 IU per kg body weight of the child by weekly intravenous-drip infusion.However, this drug is not applicable in the treatment of mucopolysaccharidosis type 2, as the active ingredient is unable to penetrate the blood-brain barrier.