Organic acidemias are clinical-biochemical entities characterized by the accumulation of organic acids in the tissues and fluids of the body, such as plasma, cerebrospinal fluid, and urine. Three clinical forms are described: severe or acute (neonatal presentation or intoxication type), chronic intermittent (late onset), and chronic or late (slow progression). These diseases are due to congenital metabolic errors in the common pathway of propionate metabolism and specific deficiencies in the catabolism of branched-chain amino acids with autosomal recessive transmission.
The clinical manifestations of organic acidemias are nonspecific and common to all. The excess of methylmalonyl-CoA and propionyl-CoA competes with acetyl-CoA in the synthesis of fatty acids, which may explain the presence of hypoglycemia, hyperglycemia, hyperlactatemia, and hyperammonemia. Isovalerylic acidemia, derived from the deficiency of the enzyme isovaleryl-CoA dehydrogenase, causes the accumulation of 3-methylcrotonyl-CoA due to inadequate metabolism of leucine, and patients may present mutations in genes related to cobalamin synthesis.
Methylmalonic acidemia occurs due to congenital errors in the metabolism of branched-chain amino acids and is characterized by the accumulation of methylmalonic acid in physiological fluids. In propionic acidemia, the deficiency of propionyl-CoA carboxylase prevents the conversion of propionyl-CoA into D-methylmalonyl-CoA. These diseases require diagnosis through enzymatic studies and molecular genetic tests.
The most common organic acidemias present diverse clinical manifestations, ranging from drowsiness and seizures to coma. The treatment of these acidemias, especially in neonatal cases or during decompensation, is a vital emergency that includes measures such as hydration, micronutrient supplementation, rapid elimination of toxins, and other specific measures depending on each case. The prognosis is often guarded, requiring strict monitoring of patients and thorough clinical, dietary, and biochemical follow-up.
