Symptoms of folic acid deficiency

Clinically, folic acid deficiency (insufficiency) in children is manifested by increasing lethargy, anorexia, low weight gain, and a tendency to gastrointestinal disorders (chronic diarrhea is possible). Glossitis, increased frequency of infectious diseases, and, in advanced cases, thrombocytopenic bleeding may be observed. There are no neurological disorders, unlike vitamin B ₁₂ deficiency. However, it has been noted that in the presence of psychoneurological disorders (epilepsy, schizophrenia), folate deficiency aggravates their course.

Congenital folate malabsorption

Rare (13 cases described); inherited in an autosomal recessive manner; characterized by selective folate malabsorption. Megaloblastic anemia develops in the first months of life, as well as diarrhea, stomatitis, glossitis, developmental delays, and progressive neurological disorders. Laboratory tests reveal very low levels of folic acid in serum, erythrocytes, and cerebrospinal fluid; urinary excretion of formiminoglutamate and orotic acid may be increased. Treatment: oral folic acid at a dose of 5-40 mg per day, if necessary, the dose may be increased to 100 mg per day or more; intramuscular administration of folic acid is also possible; to prevent relapses, folic acid is administered intramuscularly at 15 mg every 3-4 weeks.

Methyltetrahydrofolate reductase deficiency

It is inherited in an autosomal recessive manner; there are descriptions of more than 30 cases of the disease in the literature. The first clinical manifestations of the disease are noted either in the first months of life, or much later - at 16 years and older. Characteristic signs: delayed psychomotor development, microcephaly, at an older age - gait and motor disorders, strokes, psychiatric manifestations. Megaloblastic anemia is absent. Enzyme deficiency leads to an increase in plasma homocysteine and homocystinuria and a decrease in plasma methionine levels. According to the results of pathomorphological studies carried out in patients with severe deficiency of methyltetrahydrofolate reductase activity, vascular changes, thrombosis of cerebral veins and arteries, dilation of the cerebral ventricles, hydrocephalus, microgyria, perivascular changes, demyelination, macrophage infiltration, gliosis, astrocytosis, degenerative changes in the spinal cord were revealed. Demyelination can also be caused by methionine deficiency. For diagnostics, enzyme activity is determined in liver cells, leukocytes and fibroblast culture.

Prognosis: unfavorable at early onset of the disease. Treatment: the disease is resistant to therapy; folic acid, methyltetrahydrofolate, methionine, pyridoxine, cobalamin, betaine are prescribed. Prenatal diagnosis of enzyme deficiency is possible (amniocentesis, chorionic biopsy). After diagnosis, betaine is prescribed, which helps to reduce homocysteine levels and increase methionine levels.

Thiamine-dependent megaloblastic anemia

It is very rare; inherited in an autosomal recessive manner. Patients have megaloblastic anemia, and may have sideroblastic anemia with ringed sideroblasts. Leukopenia and thrombocytopenia are present. In addition to megaloblastic anemia, patients have diabetes mellitus, optic nerve atrophy, and deafness. Serum cobalamin and folate levels are normal, and there are no signs of thiamine deficiency.

The pathogenesis of the disease is unclear. It is believed that the disease may be caused by either a disorder of thiamine transport or a deficiency in the activity of the thiamine-dependent enzyme pyrophosphokinase.

Treatment: the use of vitamin B ₁₂, folic acid is ineffective. Thiamine is prescribed at 100 mg per day orally daily until the hematological parameters are completely normalized, then maintenance therapy with thiamine is carried out at 25 mg per day. If the drug is discontinued, a relapse of the disease occurs after several months.

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