GLYCOGENOSES (glycogenosis, singular; a glycogen + - osis; synonym: glycogenous disease, glycogenous accumulation) — group of the hereditary enzymopathies arising in connection with deficit of enzymes, catalyzing processes of disintegration or synthesis of a glycogen, and which are characterized by its excess accumulation in various bodies and fabrics.
For the first time the patient with a glycogenosis was described in 1910 Mr. of Lerevouillet. In 1928 S. van Creveld described a wedge, a picture G. I of type, and in 1929. To awnless wheat (E. von Gierke) a pathoanatomical picture of this disease, having established at it accumulation of a glycogen in a liver and kidneys. The first enzimol, the research G. is executed in 1952. I. G. Pompe.
G.'s prevalence in population makes 1: 40 000. 12 types G. are allocated, are fullestly studied by 9 (tab. 1); types X (the isolated G. of heart) and XI (deficit of a fosfofruktokinaza), perhaps, are options of the main forms G.
- 1 Types of glycogenoses
- 1.1 The glycogenosis of the I type
- 1.2 The glycogenosis of the II type
- 1.3 The glycogenosis of the III type
- 1.4 The glycogenosis of the IV type
- 1.5 The glycogenosis of the V type
- 1.6 The glycogenosis of the VI type
- 1.7 The glycogenosis of the VII type
- 1.8 The glycogenosis of the VIII type
- 1.9 The glycogenosis of the IX type
- 1.10 The combined types of a glycogenosis
- 1.11 not identified types of a glycogenosis
- 2 The differential diagnosis
- 3 Treatment
- 4 Table 1. Types of glycogenoses and their characteristic
- 5 Table 2. Euzymatic defects at a glycogenosis of the III type (Gardner, 1969)
Types of glycogenoses
Distinguish three main forms G.: hepatic, muscular and generalized.
The glycogenosis of the I type
the Glycogenosis of the I type (a disease to Awnless wheat, gepatonefromegalny G.) is connected with deficit of activity of glyukozo-6-phosphatase of a liver and kidneys that can be established with the help gistokhy, researches of the material received at a biopsy of these bodies during lifetime. It is inherited on autosomal recessively type. On a clinical picture this disease is carried to a hepatic Form. Its first manifestations — lack of appetite, vomiting, hypoglycemic spasms (coma), respiratory distress syndrome (see), intermittent temperature increase, hepatomegalia, nephromegaly, steatorrhea (see), a ketonuria (see. Acetonuria ) — come to light at once after the birth or at chest age. With age also a nephromegaly due to glycogenous infiltration (fig. 1), lag in growth, the disproportion of a body (the big head, a short neck and legs), the doll person, hypotonia of muscles progress gepato-; the hypoglycemic syndrome on an empty stomach accrues (patients are forced to eat almost constantly food). Often joining consecutive infections sharply strengthen ketoacidosis (see. Acidosis ) and hypoglycemia (see) and quite often are a cause of death. The hemorrhagic syndrome, a skin xanthomatosis are less often observed. Psychological development satisfactory; puberty considerably is late. The condition of patients improves in the pubertal period a little.
Biochemical, disturbances: hypoglycemia, ketosis, hyper lactacidemia, hyperlipemia, increase in blood of level not esterified fat to - t, a glycogen, cholesterol, uric to - you, disturbance of renal clearance for a number of substances. The intolerantnost to glucose is found. Administration of adrenaline, a glucagon, galactose causes a considerable hyper lactacidemia, but not a hyperglycemia since glyukozo-6-fos-fataza in a liver is absent.
The final diagnosis is made as a result of a research of activity of glyukozo-6-phosphatase in a liver by an intravital biopsy. F. van Hoof with coauthors in 1972 suggested to use for diagnosis of the I type G. marked on 14 With and 3 H glucose.
The forecast is defined by extent of decrease of the activity of enzyme. Children perish from an atsidotichesky coma or from intercurrent diseases.
The glycogenosis of the II type
the Glycogenosis of the II type (a disease to the Pomp, a generalized glycogenosis, cardiomegalia glycogenica) develops in connection with deficit acid alpha 1,4 - glucosidases. Inheritance is autosomal and recessive, communication with the frequency of emergence of an endocardial fibroelastosis is noted [Dinskoy (M. of Y. Dinscoy) et al., 1965].
At a pathoanatomical research deposits of a glycogen in all bodies and fabrics are found. The sizes of heart are increased due to glycogenous infiltration of muscle fibers (fig. 2). Organic changes in the valve device of heart are not noted. Adjournment of a glycogen in muscle fibers of language quite often leads to a macroglossia, in muscle fibers of peloric department of a stomach — to a pylorospasm, in a diaphragm and other respiratory muscles — to respiratory insufficiency. A liver, a spleen and kidneys evenly at size. On a wedge, a picture this disease is carried to a generalized Form. The first symptoms come to light in several days or weeks (up to 6 months) after the birth: cyanosis (the general and intermittent), the disorder of breath (accelerated, superficial), concern, apathy and an adynamia. Later the macroglossia, a miogipotoniya join. Early the hepatomegalia, a pylorospasm develops. Further a cardiomegaly (spherical heart, changes of an ECG), short wind, bronchitis, atelectases, hypostatic pneumonia, a myodystrophy, a hyporeflexia, bulbar disturbances, spastic paralyzes become leaders in a wedge, a picture. Lack of appetite, a growth inhibition is noted.
In blood serum contents uric to - you, glutamine-shchavelevo-acetum transaminase and zymohexase is increased; in muscles, a liver, leukocytes — deficit acid (lizosomalny) alpha 1,4 - glucosidases, the maintenance of a glycogen in a liver — 12%, in muscles — 10%. Early there is a generalized adjournment of a glycogen.
Along with a generalized form the cases caused by deficit of acid alpha glucosidase only in muscles meet. In these cases the disease is, as a rule, shown at later age and on a wedge, reminds a picture muscular Forms.
The research of the fabric received at a biopsy is solving in diagnosis biochemical. Generalized character of G. of the II type allows to define activity of glucosidase in uniform elements of blood and in skin of the patient, and also in culture of cells of fibroblasts of skin and muscles of the patient.
The prenatal diagnosis based on biochemical, is following of the cells of the exfoliated epithelium of skin of a fruit which are in an amniotic fluid is possible.
The forecast at a generalized form adverse, patients perish on the first year of life from heart or respiratory failure. At accumulation of a glycogen only in skeletal muscles forecast more favorable.
The glycogenosis of the III type
the Glycogenosis of the III type (Cory's disease, Forbes's disease, lemitdekstrinoz, debrancher enzyme defect) is caused by total or partial absence of activity of amilo-1,6-glucosidase and (or) oligo-1,4-1,4-transglucosidase. 4 subtypes of a disease (tab. 2) are established. The genetic analysis of this type G. is difficult because of existence of several of its forms. On a wedge, a picture carry to a muscular or hepatic Form.
On a wedge, reminds a picture G. of this type G. of the I type: the hepatomegalia from first months of life, a hypomyotonia, a hypertrophy of separate muscular groups, a hypertrophy of a myocardium, disturbance of cordial conductivity and blood circulation is observed. At biochemical, researches the hypoglycemia on an empty stomach, a ketosis, a lipemia, increase in level of a glycogen in erythrocytes is noted. Splitting of a glycogen is late (see tab. 1).
Definition of activity of amilo-1,6-glucosidase and oligo-1,4-1,4-transglucosidase in muscles and a liver allows to establish a form.
Forecast, as a rule, favorable. After 5-year age and especially in the pubertal period development of a disease is considerably slowed down.
The glycogenosis of the IV type
the Glycogenosis of the IV type (Andersen's disease, amilopektinoz, a diffusion glycogenosis with cirrhosis, branching enzyme defect) is caused by absence alfad-1,4-glucan, 6 - alpha glucosyltransferase. The autosomal and recessive or connected with a floor mode of inheritance is supposed.
The disease is shown from first years of life and characterized by a gepatosplenomegaliya, development of cirrhosis, jaundice, a hypoglycemia.
Forecast bad. Patients usually perish on the first year of life.
The glycogenosis of the V type
the Glycogenosis of the V type (Mac-Ardla's disease, miofosforilazny insufficiency) develops in connection with deficit of muscular phosphorylase. Activity of hepatic phosphorylase is not changed. Autosomal and recessive mode of inheritance. Males are ill 5 times more often. Due to the glycogenous infiltration skeletal muscles increase in volume, become sharply dense. On a wedge, a picture the disease is carried to a muscular Form. Its symptoms — muscular weakness, muscular spasms, tachycardia — appear in the first ten days of life and progress. There is a tranzitorny myoglobinuria [Mac-Ardl (V. of MacArdle), 1951; Pearson (S. M. Pearson) with sotr., 1961]. Concentration of a lactate in blood decreases after physical. loadings. The final diagnosis is possible at a research of phosphorylase activity in muscular bioptata; in homogenates of muscles the glycogen does not turn into a lactate.
The forecast for life favorable, recovery is impossible.
The glycogenosis of the VI type
the Glycogenosis of the VI type (Gers's disease, gepatofosforilazny insufficiency) is caused by insufficiency of phosphorylase in a liver. The autosomal and recessive mode of inheritance is supposed. On a wedge, a picture carry to a hepatic Form. A considerable hepatomegalia as a result of glycogenous infiltration of hepatocytes, the growth inhibition, the doll person, a hyperlipemia, a hyperglycemia (after intravenous administration of a galactose), the increased maintenance of a glycogen in erythrocytes are characteristic. The forecast is doubtful.
The glycogenosis of the VII type
the Glycogenosis of the VII type (Thomson's disease) develops in connection with deficit of phosphoglucomutase in a liver and (or) muscles. It is for the first time described in 1963 by W. H. S. Thomson with coauthors at the boy with a myopathy. In 1964 Illingvort (V. Illingworth) and Brown (D. N of Brown) described the boy, sick G. with a hepatomegalia. Meets seldom.
The glycogenosis of the VIII type
the Glycogenosis of the VIII type (a disease of Tarui, miofosfofruktokinazny insufficiency) is caused by deficit or total absence of activity of a fosfofruktokinaza in muscles. 6 cases of this type G. are described [Tobine et al., 1973]. On a wedge, reminds a picture G. of the V type: muscular weakness, exhaustion and lack of a hyper lactacidemia after physical. loadings. Low level of a fosfofruktokinaza in patients is found in muscles, in their parents — in erythrocytes. Forecast favorable.
The glycogenosis of the IX type
the Glycogenosis of the IX type (a disease of Haga) develops in connection with deficit of a kinase of phosphorylase b. It is inherited on the recessive, connected with a floor type. On a wedge, a picture carry to a hepatic Form. At patients the hepatomegalia is observed. Other symptoms characteristic of a hepatic form are not expressed. The forecast is unknown.
The combined types of a glycogenosis
In literature are described the separate cases which are characterized by a combination of absence glyukozo - 6 - phospha - Tazy with limitdekstrinozy [A. Calderbank et al., 1960], deficit of glyukozo-6-phosphatase with branching enzyme [Berkoff et al., 1962], etc.
not identified types of a glycogenosis
according to Illingvort and Brown (1964), Van-Hofa et al. (1972), etc., apprx. 1/3 cases of patients with a hepatic form G. could not be identified.
Cases of not identified G. of a muscular form are known (V. M. Kazakov and soavt., 1971, V. S. Lobzin and soavt.,
1973, A. A. Shutov and soavt., 1974). In 1970 L. O. Badalyan with employees observed 2 cases, on a wedge, a picture similar to G. of the V type. However activity of phosphorylase, amilo-1,6-glucosidase, phosphoglucomutase, acid maltase was normal. Activity of a hexokinase in erythrocytes was sharply reduced.
The differential diagnosis
the Differential diagnosis at newborns is carried out with syphilis (see), toxoplasmosis (see), cytomegaly (see), diseases of a liver, at more advanced age — with diseases to Gosha (see. to Gosha disease ), Nimanna — Peak (see. Nimanna-Pika disease ), tumors of a liver, myatonia (see), xanthomatosis (see).
Neuromuscular disturbances can imitate the progressing muscular dystrophy, neural amyotrophy of Sharko — Mari, spinal amyotrophy of Verdniga — Goffmanna (at generalized G. of the II type) in this connection carrying out corresponding biochemical, and morfol, researches in each case of damage of muscles is necessary.
there is no Specific treatment. Pathogenetic therapy is directed to fight with acidosis (see), ketosis. Use of a glucagon, anabolic and steroid hormones is in certain cases effective. Frequent meals with the high content of easily assimilable carbohydrates are necessary at a hypoglycemic syndrome. There are attempts of administration of missing enzymes by the patient.
At muscular G. improvement is noted after purpose of fructose inside on 50,0 — 100,0 g a day, vitamins, ATP. Attempts of surgical treatment of I and III types G. become (a porto-caval transposition of vessels, bandaging of a portal vein and imposing of an anastomosis the end sideways — v. portae and v. cava inf.).
See also Enzymopathies .
Table 1. Types of glycogenoses and their characteristic
Table 2. Euzymatic defects at a glycogenosis of the III type (Gardner, 1969)
Bibliography: Badalyan L. O., Tabolin V. A. and Veltishchev Yu. E. Hereditary diseases at children, M., 1971; Biochemical diagnosis of hereditary diseases, under the editorship of E. L. Rosen-feld and T. T. Berezov, M., 1974; V. A IAC-kyyusik. Ancestral features of the person, the lane with English, page 347, M., 1976, bibliogr.; The multivolume guide to pediatrics, under the editorship of Yu. F. Dombrovskaya, t. 10, page 87, M., 1965; Molecular bases of pathology, under the editorship of V. N. Orekho-vich, page 80, M., 1966; Rachev L., Todorov Y. of an istatev of St. A metabolism at children's age, the lane with bolg., page 265, Sofia, 1967; X and r r and since. Fundamentals of biochemical genetics of the person, the lane with English, page 170, M., 1973; Carbohydrate metabolism and its disorders, ed. by F. Dickens a. o., v. 2, p. 151, L. — N. Y., 1968, bibliogr.; Garrod A. E. Garrod’s inborn errors of metabolism, L., 1963; The metabo - * lie basis of inherited disease, ed. by J. B. Stanburg a.'o., N. Y., 1972; S i d-b u of at J. B. The glycogenoses, in book: Endocrine and genetic diseases of childhood, ed. by L. I. Gardner, p. 853, Philadelphia — L. 1969, bibliogr.
Yu. A. Knyazev; L. O. Badalyan (not BP.), V. V. Serov (stalemate. An.).