GARGOILIZM (fr. gargouille the stigma of a drainpipe in cathedrals of Gothic architecture decorated with fantastic figures with ugly persons; synonym: multiple Dysostosis, lipokhond-rodistrofiya, polydystrophy, osteochondrodystrophy) — the disease caused by heavy hereditary pathology of connecting fabric, which is shown the combined defeat of bone and joint system, an eye, internals and a nervous system. It is for the first time described by Gunter (S. Hunter, 1917) and Gurler (G. Hurler, 1919). Ellis (R. Ellis, 1936) offered the term «gargoilizm» because of characteristic outward of patients.
Carry the first two types to G. mukopolisakharidoz (see) — syndrome Gurler and Gunter's syndrome. Jervis (G. A. Jervis, 1950) established that the syndrome Gurler is observed more often than other mukopolisakharidoz (1: 10 000 births). According to WHO data (1968), Gunter's syndrome meets in 1 case on 200 000 births.
An etiology and a pathogeny
Gurler is characteristic Of a syndrome an autosomnoretsessivny mode of inheritance, at Gunter's syndrome — inheritance recessive, linked to a floor.
It is established that G. are the cornerstone genetically caused disturbances of exchange of acid mucopolysaccharides (see), the structures connected with disturbance, their excess accumulation in body tissues and the increased removal with urine. A certain value in a pathogeny of mukopolisakharidoz is allocated for the enzymes participating in splitting of acid mucopolysaccharides. D. O'Brien with sotr. (1969) and Okkerman (P. A. Ockerman, 1969) reported about deficit of a beta galactosidase in a liver and increase in its activity in plasma and urine of patients. Allocated with Dorfman and Lorints (A.Oorfman, A. Lorincz, 1957) and Meyer (K. Meuyeg, 1958) from urine of patients at a syndrome Gurler acid mucopolysaccharides were mix of a geparansulfat and dermatansulfat, total quantity reached them 150 mg and more in days. Normal excretion of acid mucopolysaccharides with urine does not exceed 10 mg in 1 days.
A number of authors indicates dominance at a syndrome Gurler a dermatansulfat, others — a geparansulfat. V. Mac-Kyyuzik (1965) and Masculine Gusev (1972) consider that at G. these mucopolysaccharides can be emitted in different ratios, at the same time prevails and excretion of a dermatansulfat amplifies with age, high excretion with urine of hondroitinsulfat is found.
At sick G. considerable changes of metabolism of lipids, preferential glycolipids (sulfatides), cholesterol and separate fractions of phospholipids are revealed. Most jumps are noted at a syndrome Gurler. Disturbance of exchange of collagen also is characteristic that is shown by the low content of oxyproline (see. Prolin ) in urine (norms are 2 — 3 times lower). There are disturbances in exchange of other amino acids — the excess content in urine of serine and threonine, the polypeptides and mucopolysaccharides participating in bonds.
The pathological anatomy
At morfol, a research comes to light defeat of various bodies and systems with accumulation of high-molecular substances lipoid polisakharidnoy the nature. These substances are laid in the form of fine-grained weight in cells of a brain, retina of eyes, peripheral nervous gangliyev. Nervous cells are represented bulked up, increased in sizes, the kernel is shifted to the periphery. Nissl's substance disappears or decreases, only the remains shifted aside together with a kernel are visible. The firm meninx is usually thickened. Homogeneous granular masses is postponed also in cells of basic fabric, a cornea, internals (a liver, a spleen, an epithelium of distal departments of gyrose tubules of kidneys).
In cells of a liver and kidneys along with acid mucopolysaccharides a significant amount of neutral fats is postponed. Change of bones — disturbance of an endostosis, growth of blood vessels in a cartilage and accumulation in its cells of acid mucopolysaccharides and lipids is characteristic. In interstitial substance of connecting fabric only soluble mucopolysaccharides come to light, lipoid substances are not found. Morphologically disorganization of structure of the main substance, a thickening and homogenization of collagenic fibers comes to light. Substantially the brain, a liver, a spleen, eyes suffer. Changes in heart valves, an aorta, blood vessels of a brain are observed patol.
At a syndrome Gurler the patient has characteristic outward. On the first year of life changes of a configuration of a skull, typical for this disease, deformation of a backbone (fig. 1) develop. These changes are often regarded as symptoms of rickets. By one year the condition of patients worsens, the lumbar kyphosis and a tutopodvizhnost of joints sharply amplify. Children lag behind in physical. and intellectual development. After one year the wedge, symptoms become especially expressed. Are characteristic of sick G.: the sunk-down nose bridge, the hung forehead, full lips and language, widely placed teeth, deformation and increase in sizes of a skull, lag in growth, nizhnegrudny and a lumbar kyphosis, deformation of a thorax, a tutopodvizhnost of joints, umbilical and inguinal hernias, gepato-and a splenomegaly, changes from heart (systolic noise, muting of tones, expansion of borders of heart).
On an ECG diffusion damage of a myocardium comes to light. Defeat of an organ of sight is observed at all patients and is the earliest and typical symptom of a disease.
At most of patients opacification of a cornea develops, a cut arises in deep layers, and then diffuzno takes all cornea (fig. 2). In some cases opacification of a cornea can be revealed since the birth. A megalokornea, inborn glaucoma, developments of stagnation and an atrophy of optic disks, pigmental dystrophy of a retina are quite often observed.
Considerable changes are observed from a nervous system; sharply expressed gipertenzionno-gidrotsefalny syndrome, changes of a muscle tone and tendon jerks, sometimes come to light pyramidal signs, in some cases — damage of cranial nerves (squint, a nystagmus), vegetative and trophic frustration (excess food, a hypertrichosis), endocrine changes (myxedema).
Mental disorders are shown by weak-mindedness, a cut reaches usually expressed degree (up to an idiocy), is followed by disturbances of the speech and sometimes decrease in hearing. At patients the raised exhaustion of a nervous system is observed, sometimes there are epileptiform attacks.
Most of researchers, that at G. there is a progressing accumulation in cells of various bodies, including a brain patol, products of the broken exchange, considers weak-mindedness at G. as result of progreduated process and carries it to acquired to weak-mindedness (see). In favor of such point of view testifies first of all the course of a disease, the first signs to-rogo appear after the birth and further steadily accrue, including weak-mindedness. Unlike an oligophrenia, weak-mindedness at G. is characterized by mosaicity. In particular, discrepancy between extent of decrease in intelligence and disturbance of activity is noted, edges owing to weakness of motives it is upset rather more. Preferential frustration mechanical (but not associative) memories, asthenic and epileptiform manifestations also correspond to organic dementia, than a true oligophrenia more.
The syndrome Gunter and proceeds more favorably. The wedge, symptoms of a disease are shown usually in 3 — 4 years. Till 1 year children develop normally. Early changes of a skeleton in the form of increase in the sizes of a skull are characteristic. The Tutopodvizhnost and changes of a shape of joints become expressed by 3 years, changes of a skeleton as deformation of a thorax and a backbone moderate.
Patients lag behind in growth to a lesser extent, than at a syndrome Gurler. Features are less rough. Gepatosplenomegaliya and a lumbar kyphosis at a number of patients are absent. Heart diseases can come to light. Existence of umbilical and inguinal hernia, decrease in hearing is characteristic. Opacification of a cornea is absent or is expressed slightly, the megalokornea, stagnation and an atrophy of disks of optic nerves, pigmental dystrophy of a retina often comes to light. Decrease in intelligence is expressed to a lesser extent, than at a syndrome Gurler.
the Diagnosis is based on a wedge., rentgenol, and datas of laboratory. Great diagnostic value has biochemical, a research of urine of patients on acid mucopolysaccharides: Berry's reaction with toluidine blue, a precipitation test with tsetavlony, with albumine (see. Express methods ). Separate fractions of acid mucopolysaccharides can be studied by means of ion-exchange chromatography and paper electrophoresis or an atsetattsellyuloza.
At G. hondroitinsulfata are allocated in large numbers dermatansulfat, geparansulfat, and also. With age excretion with urine of a dermatansulfat increases.
Detection of meta chromatic granulations in leukocytes of blood and cells of marrow (Rayleigh's granule) can have diagnostic value.
Along with a wedge, and biochemical, sick G.' research studying of a family tree and establishment of a mode of inheritance, and also a research of excretion of acid mucopolysaccharides in urine of parents and relatives of patients at whom fractional composition of acid mucopolysaccharides can be changed is necessary.
Studying of culture of fibroblasts is of great importance for detection of a heterozygous carriage.
In typical cases of G. is without effort distinguished according to roentgenograms.
The disease is characterized by generalized symmetric defeat of an epiphysis of bones. They are flattened and increased. Metadiaphyseal departments of long and short tubular bones are shortened and thickened. Valgus deformation of proximal departments of femurs (fig. 3) is typical. Flat bones are deformed, thickened, joint hollows are flattened. Edges are also thickened, their front ends is club-shaped are expanded. Necks of edges remain normal. Intercostal spaces are narrowed. The backbone is always affected, the platyspondylia and an angular kyphosis in nizhnegrudny and verkhnepoyasnichny department (fig. 4) take place. The underdevelopment of an anterosuperior corner of bodies of vertebrae, usually Th12 or L1-2 is pathognomonic. Intervertebral spaces are not narrowed. There is a disproportion in development front and a neurocranium. The base of skull is shortened. The Turkish saddle is flattened, extended, front wedge-shaped shoots are underdeveloped. Bones of a front part of a skull, especially upper jaw and nasal bones, are underdeveloped. The pnevmatization of adnexal bosoms of a nose is late. Rates and the sequence of ossification change, bone formation occurs asymmetrically.
Differential diagnosis at early stages of a disease it is necessary to carry out with inborn hydrocephaly (see), rickets (see), hypothyroidism (see), lipoidoses (see). Differential diagnosis is carried out also with other forms chondrodystrophias (see) and epiphyseal dysplasia. At them, unlike G., the normal thickness of a diaphysis of tubular bones is noted. An epiphysis has irregular shape, is increased, outlines their uneven, the structure is fragmented. The isodactylism is typical. Basin is deformed, pressed from sides, acetabular hollows are located more deeply, flattened. Unlike G. varus Deformation of femurs is observed, the system brakhispondiliya and an angulation of vertebrae is defined. At the same time deformation of one or two vertebrae in the form of a cone-shaped, wedge-shaped point of front department of bodies in nizhnegrudny or verkhnepoyasnichny departments is pathognomonic.
is reasonable purpose of hormonal drugs, in particular the glucocorticoid hormones and AKTG interfering synthesis of acid mucopolysaccharides. Use of Thyreoidinum in connection with the hypofunction of a thyroid gland which is noted at patients is effective.
Some authors suggested to apply Thyreoidinum in combination with radiation of a hypophysis. Improvement at the combined use of Thyreoidinum and Prednisolonum is possible.
Attempts of treatment of mukopolisakharidoz are made by high doses of vitamin A. Besides, apply excitants: glutaminic to - that, Cerebrolysinum, Aminalonum (Gammalonum), vitamins of group B. In the presence of convulsive attacks appoint anticonvulsants, at an adynamy — fortifying therapy. Considering the lowered body resistance of sick G., it is necessary to preserve them against infectious and other intercurrent diseases.
the Disease steadily progresses. The lethal outcome comes from respiratory diseases and a cordial decompensation. The heaviest is the first type of a mukopolisakharidoz (a syndrome Gurler) which is characterized by the progressing current and the early death of patients (the majority perishes to 10 — 12 - years - it age). Mukopolisakharidoz of the second type (Gunter's syndrome) proceeds less zlokachestvenno — patients live up to 30 and more years. During the performing early therapy the forecast more favorable.
to the Parents having the sick child is recommended to refrain from a further child-bearing. Pre-natal diagnosis of a disease on the third month of pregnancy by a research of culture of cells of the amniotic fluid received at is possible amniocentesis (see).
Bibliography: Badalyan of L, O., Gusev E. I. and Guseva M. R. Genetically determined mukopolisakharidoza at children, Pediatrics, No. 3, page 58, 1971.; Badalyan L. O., Tabolin V. A. y In e of l t and shch e in KK E. Hereditary diseases at children, page 301, M., 1971; usev E. I. Clinical and biochemical studying of some hereditary diseases of a metabolism with defeat of a nervous system, Zhurn, a neuropath, and пс:№-хиат., t. 71, No. 10, page 1475, 1971; At - E. Y. sowing y other Kliniko-biokhimicheskay and the morphological characteristic muv kopolisakharid, Vestn. USSR Academy of Medical Sciences, JMI 3, page 85, 1976, bibliogr.; Clinical psychiatry, under the editorship of G. Grule, etc., the lane with It., page 658, M., 1967; Kosinskaya of N, Page. Disturbances of development kost - but - the joint device, page 44, L., 1966, bibliogr.; The multivolume guide to pediatrics, under the editorship of Yu. F. Dombrovskoy, t. 10 * page 585, M., 1965; P e y N e r of Page 4-Radiodiagnosis of diseases of bones and joints, t. 1, page 404, M., 1964; With at x are of e in and G. E. Clinical lectures on psychiatry of children's age, t. 3, page 111, M., 1965; Brant e G. Gargoylism, Scand. J. clin. Lab. Invest., v. 4, p. 43, 1952; Hunter C. A rare disease in two brothers, Proc. roy. Soc .Med., v. 10, p. 104, 1917; Hurler G. tiber einen Typ mul-tipler Abartungen, vorwiegend am Skelet-tsystem, Z, Kinderheilk., Bd 24, S. 220, 1919; McKusick V. A. Heritable disorders of connective tissue, St Louis, 1972; it, The nosology of the mucopolysaccharidoses, Amer. J. Med., v. 47, p. 730, 1969; M e at e of To. Biochemistry and biology of mucopolysaccharides, ibid., p. 664; OrendiK. Knochen-, Gelerik-und Weich-teilerkrankungen im Rontgenbild, Jena, 1968, Bibliogr.; Rubin P. Dynamic classification of bone dysplasia, Chicago, 1964.
BB. E. Veltishchev, E. I. Gusev, M. R. Guseva; M. S. Vrio (psikhiat.), M. K. Klimova (rents.).