Fabri's disease
Contents:
Description:
Fabri's disease (Fabry, a diffusion universal angiokeratoma, a hereditary dystonic lipidosis) - the inborn disease which is characterized by the hereditary deficit of enzyme of alpha G4 galactosidase leading to accumulation of glycolipids (ceramide) in cytoplasm and lysosomes of cells of various bodies and fabrics.
It is described for the first time in 1898 by the English dermatologist Anderson and the German dermatologist Fabry.
Fabri etiologies:
Fabri's disease is caused by insufficiency of lysosomic hydrolase - a-galactosidases And, is inherited on the H-linked recessive type in this connection the clinical symptomatology is shown at males. The gene of an a-galactosidase And is localized on a long shoulder of X-chromosome of Xq22 ® by q24.
Pathogeny:
Enzymatic defect leads to system adjournment of sfingoglikolipid and a glycoprotein in the struck fabrics, in particular in an endothelium and smooth muscles of vessels, heart, kidneys (renal balls and tubules), eyes (epithelial cells of a cornea), gangliya of the autonomic nervous system.
Symptoms of a disease of Fabri:
At homozygous men the disease is shown at children's age or at teenagers the so-called crises of Fabri which are characterized by the painful burning palm pain and feet Attacks of pains several days can last, be followed by small fever and increase in SOE. Sometimes rheumatism is mistakenly diagnosed. Akroparasteziya become more frequent and heavy with age. At children's age damages of skin, characteristic of Fabri's disease, - angiokeratomas (teleangiectasias or small superficial angiomas) which are localized symmetrically on hips, a back, buttocks, external genitals, in the field of knee joints and a navel are noted. Angiokeratomas can be flat or a little towering over the surface of skin, from dark red till bluish-black color, do not turn pale when pressing. Hypo - or a skin anhidrosis is characteristic. Perhaps also damage of a mucous membrane of an oral cavity and conjunctiva. Expansion and tortuosity of a retina and conjunctiva, opacification of a cornea are observed. With age accumulation of sfingoglikolipid and a glycoprotein in bodies of cardiovascular system and kidneys increases. There are stenocardia symptoms, heart valves (mitral insufficiency and a stenosis of an aorta) are surprised, the hypertrophy of a left ventricle, a myocardial infarction develop.
The proteinuria, decrease in filtrational ability of kidneys are observed. Development of a chronic renal failure is possible. Arterial hypertension (apparently, a renal origin) strengthens disturbances from heart and promotes defeat of brain vessels. Cerebrovascular manifestations include thrombosis, aneurisms, sometimes hemorrhages that leads to developing of spasms, a hemiplegia, aphasia; psychosis is possible. Changes from digestive tract are characterized by nausea, vomiting, diarrhea, abdominal pains. Deformation of distal interphalangeal joints, an aseptic necrosis of a head of femoral and collision bones, the expressed osteoporosis of vertebrae are noted. Hypochromia microcytic anemia, a growth inhibition and puberty are possible. Death comes from uraemia or vascular damages of heart and brain usually on the 4th decade of life.
At heterozygous women symptoms of a disease can be absent, at most of bearers of a gene of a disease of Fabri skin manifestations and opacification of a cornea are observed, sometimes symptoms of a disease are expressed the same as at men.
Skin manifestations at Fabri's disease
Diagnosis:
The diagnosis is based on clinical manifestations, detection of activity of an a-galactosidase And in plasma, leukocytes, the lacrimal liquid, the cultivated fibroblasts, bioptata of fabrics, and also increase in level of sfingoglikolipid (in particular a trigeksoziltseramida) in urine, plasma, the cultivated fibroblasts. The differential diagnosis is carried out with a hereditary hemorrhagic teleangaektaziya at which teleangiectasias in various parts of a body, bleedings are observed, but there are no attacks of pains, damage of kidneys and cardiovascular system, digestive tract, characteristic of Fabri's disease. The differential diagnosis with rheumatism is based on skin changes and distinctions of biochemical indicators, characteristic of Fabri's disease.
Treatment of a disease of Fabri:
For removal and the prevention of attacks of pains appoint diphenylhydantoin and карбамадепин, corticosteroids. In some cases transplantation of a kidney is shown. Attempts of administration of the purified enzyme, however enzyme half-life in an organism short are made.
