Symptoms of glycogenases

Glycogenosis type I

The disease can debut in the neonatal period (severe hypoglycemia and metabolic acidosis), but most often in the 3-4th month of life. The main symptoms are hepatomegaly and hypoglycemia. On examination, the children notice a large protruding belly (due to the increase in liver size), local fat deposits, mainly on the cheeks ("puppet" face), buttocks, hips, muscle hypotrophy and growth retardation. Skin xanthomas can arise on the elbows, knees, buttocks, hips. Severe hypoglycemia and lactic acidosis (increased levels of lactic acid in the blood) are provoked by delays in feeding and intercurrent infections. Despite a significant increase in size, liver function, as a rule, does not suffer. Some patients describe intermittent diarrhea of an unknown origin. In the second-third decade of life, liver adenomas with a tendency to malignant degeneration may appear. Some patients develop pulmonary hypertension, progressing to heart failure. With the glycogenesis of lb, an increase in the spleen can occur. In most patients with type I glycogenesis, neutropenia develops in the first year of life. This explains the propensity to infections (recurrent otitis media, stomatitis, gingivitis, pneumonia, respiratory tract infection, urinary tract infection, etc.). Approximately 75% of patients with lb type develop ulcers of the intestinal mucosa, chronic inflammation of the intestine.

Clinical manifestations of type III glycogenosis in children are similar to those of type I glycogenosis: hepatomegaly, growth retardation, hypoglycemia, hyperlipidemia. Some patients have splenomegaly, but unlike glycogenosis type I, the kidneys are not enlarged and their functions do not suffer. With age, these manifestations decrease and may even completely disappear to the pubertal period. Myopathy, as a rule, does not occur in children, although in some cases it is found that there is a slight hypotension and a delay in acquiring motor skills. Most often, myopathy is manifested in adults and can be distal or generalized. In patients with distal myopathy, atrophy of the muscles of the extremities is observed, often leading to peripheral polyneuropathy and motor neuron disease. Myopathy progresses slowly. In some cases, generalized myopathy with a lesion of respiratory muscles is observed. Cardiomyopathy is rare. In some patients, liver damage is so poorly expressed that the diagnosis is made with the appearance of muscle symptoms at a later age.

Glycogenosis type IV

Clinical manifestations of deficiency of the branching enzyme glycogen are quite diverse. Until recently, it was believed that the disease manifested only hepatosplenomegaly and leads to an early death on the background of liver failure. However, a number of publications describe atypical forms of the disease with slowly progressing liver pathology or with a predominant lesion of the heart muscle. It is believed that some cases of congenital myopathy can also be associated with this hereditary pathology. The neurological variant of the disease in adults (a disease with polyglucosan bodies) is similar in clinical manifestations with amyotrophic lateral sclerosis.

Patients with a classical form of the disease at an early age are diagnosed with developmental delay and hepatomegaly. Cirrhosis progresses and leads to portal hypertension, ascites, esophageal veins. Some patients develop hepatocellular carcinoma. Life expectancy is significantly reduced, and without liver transplantation, a fatal outcome occurs in the 4-5th year of life. In some cases, the disease can have a more benign course and progress more slowly.

Neuromuscular forms of glycogenosis type IV are much more diverse in clinical manifestations. In the case of a neonatal form (extremely rare), fetal akinesia, arthrogryposis deformity, fetal edema and early death are characteristic. The congenital form is accompanied by a primary lesion of skeletal and cardiac musculature; it is characterized by muscular hypotension and cardiomyopathy.

Glycogenosis of type VI

Clinical manifestations are similar to those in type IX glycogenesis; characterized by hepatomegaly and growth retardation from the first decade of life. Heart and skeletal muscles do not suffer. With age, these symptoms become less pronounced and can even completely disappear to the puberty period. There is a tendency to hypoglycemia, which is never as severe as with glycogenases I and III types. The concentration of triglycerides and ketone bodies is not significantly increased.

Glycogenosis IX type

The main clinical manifestations are hepatomegaly as a result of glycogen accumulation, growth retardation, increase in the level of hepatic transaminases, hypercholesterolemia, hypertriglyceridemia. Symptomatic hypoglycemia and hyperketonemia occur in children only after prolonged fasting. Clinical manifestations and biochemical changes tend to become milder with age, and there are no signs of disease after the puberty period.

Muscle forms of type IX glycogenosis are clinically similar to McArdle's disease and are manifested by intolerance to physical exertion, muscle pain and recurrent myoglobinuria in adolescents and adults. Less common is muscular weakness and respiratory failure at an early age. The morphological sign of the disease is subsarcolemal clusters of glycogen of normal structure.

Glycogenosis of type 0

The first symptom of the disease is fasting hypoglycemia at an early age. However, as a rule, it is asymptomatic. Recurrent attacks of hypoglycemia often lead to neurologic disorders. A large number of patients are experiencing a developmental delay, which is probably associated with periods of hypoglycemia. Hypoglycemia occurs in the morning before the first meal. Dimensions of the liver are not increased, although there may be fatty liver degeneration. In some patients growth slows down, which is restored after the start of diet therapy. A small number of patients described in the literature are more likely to reflect a small proportion of diagnosed cases, since the symptoms of the disease are not very specific, and the metabolic changes are not always interpreted correctly by the doctors.

Glycogenosis type II

There are several clinical forms. For the infantile form of the disease with a debut in the first year of life, an acute course and an early lethal outcome are characteristic. For the late form of the disease, manifested in adolescence and later, characterized by the absence of severe heart damage and a more favorable prognosis.

In the infantile form of the disease, the activity of alpha-glycosidase is practically absent. The first symptoms of the disease appear from the first months of life: feeding difficulties, low weight gain, respiratory disorders, often complicated by pulmonary infection, delayed motor development. In the majority of patients, generalized progressive muscular weakness is observed; children can not move and hold their heads on their own. Despite this, the muscles to the touch are firm, even hypertrophied. More than half of patients also notice macroglossy and mild hepatomegaly. The activity of CK is significantly increased. The majority of infants with Pompe disease develop marked and progressive cardiomegaly by the 6th month of life. The accumulation of glycogen in the myocardium causes a thickening of the walls of the ventricles and the interventricular septum, resulting in hypertrophic cardiomyopathy progressing to the dilated one. At autopsy, the heart is more than three times the size. Fibroelastosis of the endocardium is quite common. With an ECG, a shortened PR interval is detected. Often combined with a high voltage of QRS complexes. These signs are typical for the disease and can distinguish it from other early cardiomyopathies. Infantile form of Pompe disease leads to death of up to 1 year, especially if significant violations of cardiac activity are manifested in children up to 6 months of age

The late form of the disease Pompe can debut at any age - from the first years of life to adulthood. Practically all patients with manifestation of the disease after 2 years do not observe severe pathology from the heart; the defeat of the muscles progresses more slowly and the prognosis of the disease is less severe than in the infantile form. The debilitating symptoms and the involvement of internal organs in the pathological process are different in different patients, but all patients as a leading symptom note a slowly progressing muscle weakness. The proximal muscles (trunk and lower limbs) are usually affected primarily, then the diaphragm and other muscles involved in the act of breathing are involved, which leads to lung failure and respiratory depression in the dream. Disease can also appear in adulthood (from 20 to 60 years). However, many patients note a rapid fatigue and shortness of breath during physical exertion, which bothered them since childhood. In adults, the predominant symptom is a slowly progressing muscle weakness in the lower extremities involving the muscles of the trunk and / or respiratory failure. As the disease progresses, deep tendon reflexes disappear. Approximately one-third of all adult patients are characterized by respiratory failure.

Glycogenosis of type V

The disease debuts in adolescence or the 2-3rd decade of life and is characterized by intolerance to physical exertion, myalgia and muscle weakness at the time of exercise; in rest muscles are restored. These symptoms occur most often as a result of short and intense loads - running for short distances, lifting weights - and less intense, but prolonged, such as climbing stairs, walking on snow. Normal loads, such as walking on a flat surface, do not cause problems. Quite often there are painful crimps - convulsive muscle contractions. Many patients note the so-called "second breath" phenomenon - a small rest after a painful attack allows continuing physical exercise more easily. Myoglobinuria (with the risk of acute renal failure) is observed in half of the patients.

Glycogenosis type VII

Clinical manifestations of type VII glycogenosis are similar to those of type V glycogenase. In this disease, a combination of symptoms of damage to the muscular and hematopoietic tissue is observed. Patients are observed an increase in the concentration of bilirubin and the number of reticulocytes, reflecting compensated hemolysis.

Another distinctive feature is the absence of the "second breath" phenomenon, characteristic of type V glycogenase. Two clinical forms stand out: an adult with constant muscle weakness (although most patients note these disorders from adolescence) and a multisystem child with generalized muscle weakness, central nervous system damage (convulsions, cortical blindness), cardiac tissue (cardiomyopathy), and vision organ .

Glycogenosis IIb type

The disease debuts after the first decade of life and is characterized by a lesion of skeletal and cardiac muscle tissue.

Insufficiency of phosphoglycerate kinase

Clinical manifestations depend on the degree of damage to the three tissues - muscle, nerve and blood cells. There are several clinical options: a combination of nesferocytic hemolytic anemia and central nervous system damage, isolated myopathy or a combination of myopathy with a lesion of the nervous system. Myopathic forms are similar to type V glycogenesis.

Glycogenosis of the XI type

The first case of the disease was detected accidentally in a biochemical examination of a patient with myoglobinuria and a high level of CK. In all patients, intolerance to physical exertion, muscle pain and myoglobinuria are observed.

Glycogenosis of type X

Clinical manifestations - intolerance to physical exertion, muscle pain and myoglobinuria. In some cases, the disease manifests in carriers. In muscle biopsies, a moderately expressed accumulation of glycogen is detected.

Glycogenosis of type XII

Intolerance to physical activity.

Glycogenosis XIII type

The disease manifests itself at a late age with progressive intolerance to physical exertion, myalgia and elevated levels of CK.

[1], [2], [3], [4], [5]