Type III Glycogenosis (Measles Disease, Forbes Disease, Limitdextrinosis)

What is Type III Glycogenosis (Measles Disease, Forbes Disease, Limit Dextrinosis)?

Glycogenosis of the third type is associated with mutations in the structural gene of the cytosolic amylo-1,6-glucosidase, which is expressed in many tissues: liver, muscle, and red blood cells. The gene is mapped on chromosome 1p21. Like previous options, the third type of glycogenosis is inherited in an autosomal recessive manner.

Causes of Type III Glycogenosis (Measles Disease, Forbes Disease, Limit Dextrinosis)

Glycogenosis III is inherited in an autosomal recessive manner. Often parents are in kinship. In one family, sometimes a brother and sister or two brothers get sick. At the heart of the disease is a gene mutation that is detected clinically in homozygotes.

Pathogenesis during Type III Glycogenosis (Measles Disease, Forbes Disease, Limit Dextrinosis)

In a population of Sephardic Jews (natives of North Africa), the disease occurs with a frequency of 1: 5400 newborns. Amylo-1,6-glycosidase is involved in glycogen metabolism at the branch points of the glycogen “tree”. The enzyme is bifunctional: on the one hand, it converts limit dextrin to glycogen with normal outer chains and, on the other hand, releases glucose by hydrolysis of the a-1,6-glucosidic bond. Enzyme deficiency leads to disruption of glycogenolysis and the accumulation in the tissues of glycogen molecules of an abnormal shape with shortened outer chains. As with type 1 and type 2 glycogenoses, in this variant of the disease, glycogenolysis disorder is accompanied by hypoglycemia, lactate acidosis, and hyperketonemia.

Pathological anatomy. Glycogen accumulates in the liver, muscles and heart. A chemical study reveals an anomaly in the structure of glycogen (limitdextrin). Histologically revealed large swollen fibrils, subjected to vacuolization. Hepatocytes are vacuolated and look foamy, and fibrosis and squamous cell infiltration are noted in the portal spaces.

Electron microscopically, the glycogen of the liver is detected in the form of alpha and beta particles, the cell organelles are normal and are outside the accumulations of glycogen. Clinically, this type of glycogenosis resembles type I, but the symptoms are not so pronounced. Children of short stature, with a doll face and a large belly.

There is an increase in subcutaneous fatty tissue on the face and on the trunk, in connection with which the limbs look thin. An important clinical symptom is significant hepatomegaly, which is noted already in the first or second month of life. The liver grows rapidly and occupies the abdominal cavity.

Symptoms of Type III Glycogenosis (Measles Disease, Forbes Disease, Limit Dextrinosis)

Clinical manifestations vary.

There are two clinical forms with a chronic course:

  • III- in which there are symptoms of damage to the liver muscles and I
  • IIIb – in which only the liver is affected.

The disease begins at the age of 6 months to 3 years. The clinical picture in childhood is similar to that of type I glycogenosis. Typical symptoms are hepatomegaly, growth retardation, malnutrition, “doll” face, local fat deposits, skin xanthomas. Lactate acidosis with hyperketonemia during fasting is typical. Hepatomegaly with liver dysfunction, found in all patients in childhood, tends to disappear in the post-puberty period. Patients usually live to adulthood, but sudden infant death syndrome is possible. In adult patients, myopathy with progressive muscle weakness during physical exertion (sometimes in the form of a shaky gait), hypotrophy of the muscles of the distal parts of the lower extremities (mainly calf muscles) dominates, and later on, damage to the muscles of the hands joins.

Diagnosis of Type III Glycogenosis (Measles Disease, Forbes Disease, Limit Dextrinosis)

Diagnosis of the disease is carried out on the basis of the clinical picture and laboratory research data: a decrease in the activity of amyl-1,6-glucosidase and deposition of glycogen of altered structure in hepatocytes and muscles. In plasma there is an increase in the concentration of lactate, uric acid, cholesterol and triglycerides.

Treatment of Type III Glycogenosis (Measles Disease, Forbes Disease, Limit Dextrinosis)

Due to impaired glycogenolysis during type III glycogenesis, glucose production is insufficient, therefore hypoglycemia occurs in infants and young children after nightly starvation. Increased gluconeogenesis leads to a decrease in the level of amino acids in the plasma (they are used as substrates of gluconeogenesis).

Thus, the goal of treatment is to prevent starvation hypoglycemia and compensate for amino acid deficiency. It is carried out as follows:

  • taking the necessary amount of glucose in the form of raw corn starch in combination with a diet containing a sufficient amount of proteins and other nutrients eliminates metabolic disorders and growth retardation;
  • patients with severe growth retardation and severe myopathy are shown continuous overnight probe nutrition with a mixture containing glucose, oligosaccharides and amino acids, and frequent intake of protein-rich food in the daytime.