acidopathies

Acidopathies refer to a group of metabolic disorders characterized by disturbances in acid-base balance within the body, primarily involving abnormal acid accumulation or impaired acid excretion. These conditions often result from defects in metabolic pathways, renal function, or mitochondrial activity, leading to systemic acidemia—a state where the blood pH falls below the normal range (typically below 7.35).

The most common acidopathies include organic acidemias, such as methylmalonic acidemia and propionic acidemia, where toxic organic acids build up due to enzymatic deficiencies. Another significant category is the lactic acidemias, caused by impaired lactate metabolism, often linked to mitochondrial dysfunction or genetic mutations. Renal tubular acidoses (RTAs) are also acidopathies, arising from defective acid excretion in the kidneys, leading to persistent metabolic acidosis despite normal renal function in other respects.

Symptoms of acidopathies vary but may include metabolic acidosis, lethargy, vomiting, developmental delays, muscle weakness, and in severe cases, coma or organ failure. Diagnosis typically involves blood gas analysis, serum electrolyte measurements, and metabolic profiling, such as tandem mass spectrometry for organic acids. Genetic testing may confirm underlying enzymatic or structural defects.

Management of acidopathies focuses on correcting acid-base imbalances, mitigating metabolic crises, and addressing underlying causes. Treatment may include dietary modifications (e.g., restricting protein or specific amino acids), supplementation with vitamins or cofactors, and in some cases, dialysis or liver transplantation. Early diagnosis and intervention are critical to improving long-term outcomes, as untreated acidopathies can lead to progressive organ damage and neurological complications.

Acidopathies are typically inherited in an autosomal recessive pattern, though sporadic cases may occur due to de novo mutations. Research into enzyme replacement therapies, gene therapy, and novel pharmacological interventions continues to advance treatment options for affected individuals.