Causes of sideroblastic anemias

Hereditary forms

They are transmitted in a recessive, X-linked manner (males are affected) or an autosomal dominant manner (both males and females are affected).

Metabolic block may occur at the stage of formation of delta-aminolevulinic acid from glycine and succinyl CoA. This reaction requires pyridoxal phosphate, an active coenzyme of pyridoxine and aminolevulinic acid synthetase. Laboratory tests reveal low concentrations of protoporphyrin and other porphyrins in erythrocytes. In other cases, metabolic block may occur between the stages of formation of coproporphyrinogen and protoporphyrin IX, probably due to deficiency of coproporphyrinogen decarboxylase. In this case, coproporphyrin increases with decreased protoporphyrin levels in erythrocytes. Disruption of protoporphyrin and heme formation makes it impossible to use iron for hemoglobin synthesis, which leads to accumulation of iron in the body and its deposition in tissues and organs.

Clinical symptoms of the disease usually appear in late childhood. Patients develop anemic syndrome caused by hypoxia and manifestations of tissue hemosiderosis due to the deposition of iron unused for the needs of hemocytopoiesis in organs and tissues. Manifestations of anemic syndrome are lethargy, weakness, rapid fatigue during physical exertion. During examination, paleness of the skin and mucous membranes is noted, adequate to the degree of anemia. Manifestations of hemosiderosis are hepatosplenomegaly; cardiovascular insufficiency caused by iron deposition in the myocardium (patients complain of palpitations, shortness of breath, tachycardia, edema); the development of diabetes mellitus caused by iron deposition in the pancreas is possible; there may be damage to the lungs, kidneys and other organs. In some patients, the skin acquires an earthy tint.

Acquired forms

Acquired forms of anemia associated with impaired porphyrin synthesis may be caused by lead poisoning.

Household lead intoxication is quite common in pediatric practice. It occurs when eating food that has been stored in tinned or home-made clay pottery with glaze. Lead poisoning is most often caused by the ingestion of lead-containing paints, plaster, and other materials saturated with lead dyes (newspapers, gypsum, crushed stone; lead content exceeds 0.06%), as well as household dust and soil particles (lead content 500 mg/kg). Lead enters the atmosphere not only through inhalation; most often it precipitates and enters the body with dust and soil particles. In infants, lead poisoning occurs when contaminated water is used to prepare infant formula. Intoxication can result from failure to observe the necessary precautions when smelting lead at home.

In lead intoxication, the conversion of delta-aminolevulinic acid into porphobilinogen, coproporphyrinogen into protoporphyrinogen, and the incorporation of iron into protoporphyrin are disrupted. These three metabolic defects in heme synthesis are explained by the blocking by lead of the sulfhydryl groups of the enzymes involved in these stages of synthesis - mainly delta-aminolevulinic acid dehydrase and heme synthetase. As a result, there is an accumulation of delta-aminolevulinic acid in erythroid cells (and the appearance of large amounts in the urine), an increase in the content of protoporphyrin, coproporphyrinogen, and iron in them. Anemia in lead intoxication (saturnism) is also caused by increased hemolysis of erythrocytes.

The clinical picture of saturnism is characterized by symptoms of damage to the nervous system. Patients suffer from headaches, dizziness, poor sleep, irritability. Hyperkinetic syndrome and transient paresis are possible. With prolonged and severe lead poisoning, polyneuritis, encephalopathy develop, and convulsive syndrome is possible. Lead colic appears, simulating "acute abdomen". Upon examination - pale skin, an earthy-grayish tint - "lead pallor". A characteristic sign is a lead border on the gums at the necks of the teeth. Dyspeptic disorders are noted.

Acquired sideroblastic anemias may be associated with the use of certain medications: anti-tuberculosis (cycloserine, isoniazid), used in tumor therapy (melfan, azathioprine), chloramphenicol, i.e. they are secondary. The possibility of developing sideroblastic anemia while taking the medications listed above is explained by the fact that they are metabolic antagonists of pyridoxine and partially inhibit the activity of aminolevulinic acid synthetase.