Disorder of ketolysis

Disorder of ketolysis (also known as ketone body utilization defect) is a group of rare inherited metabolic conditions in which the body is unable to properly break down ketone bodies for energy. Ketone bodies (acetoacetate and beta-hydroxybutyrate) are produced by the liver during fasting or periods of metabolic stress and serve as an important alternative fuel source for the brain, heart, and skeletal muscles. When ketolysis is impaired, ketone bodies accumulate in the blood, leading to severe ketoacidosis. The primary enzyme deficiency associated with this category is succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency (also known as 3-oxoacid CoA transferase deficiency), though mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase or T2) deficiency may also be classified under this umbrella. Clinical manifestations typically present in infancy or early childhood and are characterized by recurrent episodes of severe ketoacidosis, often triggered by fasting, intercurrent illness, or physiological stress. During acute episodes, patients may experience vomiting, lethargy, tachypnea (rapid breathing), dehydration, and in severe cases, coma or death if untreated. Between episodes, patients may appear clinically well. Some patients with SCOT deficiency may exhibit permanent ketosis even in the fed state, which is a distinguishing feature. The condition primarily affects metabolic homeostasis, with secondary effects on the central nervous system and cardiovascular system during acute crises. Treatment is primarily supportive and preventive. Acute episodes of ketoacidosis require emergency management with intravenous glucose and fluid resuscitation to suppress ketogenesis and correct metabolic acidosis. Long-term management focuses on avoidance of prolonged fasting, dietary modifications including frequent carbohydrate-rich meals, and prompt intervention during illness. With early diagnosis and appropriate management, outcomes can be favorable, though recurrent severe episodes carry a risk of neurological damage. Newborn screening programs in some regions may facilitate early detection through expanded metabolic screening panels.

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