Symptoms of glycogenoses

Glycogenosis type I

The disease may debut in the neonatal period (severe hypoglycemia and metabolic acidosis), but most often in the 3rd-4th month of life. The main symptoms are hepatomegaly and hypoglycemia. On examination, children have a large protruding abdomen (due to an increase in the size of the liver), local fat deposits, mainly on the cheeks ("doll" face), buttocks, thighs, muscle wasting and growth retardation. Skin xanthomas may occur on the elbows, knees, buttocks, thighs. Severe hypoglycemia and lactic acidosis (increased lactic acid levels in the blood) are provoked by delays in feeding and intercurrent infections. Despite a significant increase in size, liver function, as a rule, is not affected. Some patients have been described as having intermittent diarrhea of unknown origin. In the second or third decade of life, liver adenomas with a tendency to malignant transformation may appear. Some patients develop pulmonary hypertension, progressing to heart failure. With glycogenosis lb, the spleen may enlarge. Most patients with glycogenosis type lb develop neutropenia in the first year of life. This explains the tendency to infections (recurrent otitis, stomatitis, gingivitis, pneumonia, respiratory tract infections, urinary tract infections, etc.). Approximately 75% of patients with type lb develop ulcers of the intestinal mucosa, chronic inflammation of the intestine.

Clinical manifestations of glycogenosis type III in children are similar to those of glycogenosis type I: hepatomegaly, growth retardation, hypoglycemia, hyperlipidemia. Some patients have splenomegaly, but, unlike glycogenosis type I, the kidneys are not enlarged and their functions are not affected. With age, these manifestations decrease and may even completely disappear by puberty. Myopathy, as a rule, does not occur in children, although in some cases minor hypotension and delayed acquisition of motor skills are detected. Myopathy most often occurs in adults and can be distal or generalized. Patients with distal myopathy have atrophy of the limb muscles, often leading to peripheral polyneuropathy and motor neuron disease. Myopathy progresses slowly. In some cases, generalized myopathy with damage to the respiratory muscles is observed. Cardiomyopathy develops rarely. In some patients, liver damage is so mild that the diagnosis is made when muscle symptoms appear at a later age.

Glycogenosis type IV

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

In patients with the classic form of the disease, developmental delay and hepatomegaly are detected at an early age. Cirrhosis progresses and leads to portal hypertension, ascites, and esophageal varices. Some patients develop hepatocellular carcinoma. Life expectancy is significantly reduced, and without liver transplantation, death occurs in the 4th to 5th year of life. In some cases, the disease may 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 the neonatal form (extremely rare), fetal akinesia, arthrogryposis-type deformations, fetal hydrops, and early death are characteristic. The congenital form is accompanied by predominant damage to the skeletal and cardiac muscles; it is characterized by muscular hypotonia and cardiomyopathy.

Glycogenosis type VI

Clinical manifestations are similar to those of glycogenosis type IX; hepatomegaly and growth retardation are characteristic from the first decade of life. Cardiac and skeletal muscles are not affected. With age, these symptoms become less pronounced and may even disappear completely by puberty. A tendency to hypoglycemia is observed, which is never as severe as in glycogenoses types I and III. The concentration of triglycerides and ketone bodies is slightly increased.

Glycogenosis type IX

The main clinical manifestations are hepatomegaly as a result of glycogen accumulation, growth retardation, increased liver transaminase levels, hypercholesterolemia, and hypertriglyceridemia. Symptomatic hypoglycemia and hyperketonemia occur in children only after prolonged starvation. Clinical manifestations and biochemical changes usually become milder with age, and after puberty, patients show no signs of the disease.

Muscle forms of glycogenosis type IX are clinically similar to McArdle disease and are manifested by intolerance to physical activity, muscle pain, and recurrent myoglobinuria in adolescents and adults. Less common are generalized muscle weakness and respiratory failure in early childhood. The morphological feature of the disease is subsarcolemmal accumulations of glycogen of normal structure.

Glycogenosis type 0

The first symptom of the disease is fasting hypoglycemia in early childhood. However, it is usually asymptomatic. Recurrent hypoglycemic episodes often lead to neurological impairment. A large number of patients have developmental delays, which are probably related to periods of hypoglycemia. Hypoglycemia occurs in the morning hours before the first meal. The liver is not enlarged, although fatty degeneration of the liver may occur. Some patients have growth retardation, which is restored after the start of diet therapy. The small number of patients described in the literature rather reflects a small proportion of diagnosed cases, since the symptoms of the disease are not very specific, and metabolic changes are not always correctly interpreted by doctors.

Glycogenosis type II

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

In the infantile form of the disease, alpha-glycosidase activity is virtually absent. The first symptoms of the disease appear in the first months of life: feeding difficulties, poor weight gain, respiratory problems, often complicated by pulmonary infection, and delayed motor development. Most patients have generalized progressive muscle weakness; children cannot move or hold their heads up on their own. Despite this, the muscles are hard to the touch, even hypertrophied. More than half of the patients also have macroglossia and moderate hepatomegaly. CPK activity is significantly increased. Most infants with Pompe disease develop severe and progressive cardiomegaly by the age of 6 months. Accumulation of glycogen in the myocardium causes thickening of the ventricular walls and interventricular septum, resulting in hypertrophic cardiomyopathy, which progresses to dilated cardiomyopathy. At autopsy, the heart size is more than three times the norm. Endocardial fibroelastosis is quite common. ECG reveals a shortened PR interval, often in combination with high voltage of QRS complexes. These signs are typical for the disease and allow it to be distinguished from other early cardiomyopathies. The infantile form of Pompe disease leads to death before 1 year, especially if significant cardiac dysfunction occurs in children under 6 months of age.

The late form of Pompe disease can debut at any age - from the first years of life to adulthood. Almost all patients with the manifestation of the disease after 2 years do not have pronounced pathology from the heart; muscle damage progresses more slowly and the prognosis of the disease is less severe than in the infantile form. The debut symptoms and the involvement of internal organs in the pathological process differ in different patients, but all patients note slowly progressing muscle weakness as the leading symptom. The proximal muscles (trunk and lower limbs) are usually affected first, then the diaphragm and other muscles involved in the act of breathing are involved, which leads to pulmonary insufficiency and sleep apnea. The disease can also manifest itself in adulthood (from 20 to 60 years). However, many patients note rapid fatigue and shortness of breath during physical exertion, which have bothered them since childhood. In adults, the predominant symptom is slowly progressive muscle weakness in the lower extremities with involvement of the trunk muscles and/or respiratory failure. As the disease progresses, deep tendon reflexes disappear. Respiratory failure is characteristic of approximately one third of all adult patients.

Glycogenosis type V

The disease debuts in adolescence or in the 2nd-3rd decade of life and is characterized by intolerance to physical activity, myalgia, and muscle weakness during exercise; muscles recover at rest. These symptoms most often occur as a result of short and intense exercise - short-distance running, lifting weights - and less intense but long-term, such as climbing stairs, walking in the snow. Normal exercise, such as walking on a flat surface, does not cause problems. Painful cramps - spasmodic muscle contractions - occur quite often. Many patients note the so-called "second wind" phenomenon - a short rest after an attack of pain allows them to continue performing physical exercise more easily. Myoglobinuria (with the risk of acute renal failure) is observed in half of patients.

Glycogenosis type VII

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

Another distinctive feature is the absence of the "second wind" phenomenon, characteristic of glycogenosis type V. There are two clinical forms: adult - with constant muscle weakness (although most patients note these disorders from adolescence) and a childhood multisystem form with generalized muscle weakness, damage to the central nervous system (convulsions, cortical blindness), cardiac tissue (cardiomyopathy) and the organ of vision.

Glycogenosis type IIb

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

Phosphoglycerate kinase deficiency

Clinical manifestations depend on the degree of damage to three tissues - muscle, nerve and blood cells. Several clinical variants are distinguished: a combination of non-spherocytic hemolytic anemia and damage to the central nervous system, isolated myopathy or a combination of myopathy with damage to the nervous system. Myopathic forms are similar to glycogenosis type V.

Glycogenosis type XI

The first case of the disease was discovered accidentally during a biochemical examination of a patient with myoglobinuria and high CPK levels. All patients have exercise intolerance, muscle pain, and myoglobinuria.

Glycogenosis type X

Clinical manifestations include exercise intolerance, muscle pain, and myoglobinuria. In some cases, the disease manifests in carriers. Muscle biopsy reveals moderate accumulation of glycogen.

Glycogenosis type XII

Intolerance to physical exertion.

Glycogenosis type XIII

The disease manifests itself in late life with progressive exercise intolerance, myalgia and elevated CPK levels.

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