Beta-ketothiolase deficiency

Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or break down the ketone bodies produced when fat is metabolized. It belongs to a broader group of ketone utilization disorders and typically becomes apparent between six months and two years of age, when a child experiences the first episode revealing the underlying metabolic vulnerability. The disorder is caused by mutations in the ACAT1 gene, which reduce or eliminate the activity of an enzyme needed to break down proteins and fats; without adequate enzyme activity, the body cannot properly process isoleucine or the ketones generated during fat breakdown, and harmful compounds accumulate while blood acidity rises. Episodes present with vomiting, dehydration, difficulty breathing, extreme tiredness, and occasionally convulsions, and in severe cases can progress to coma; these ketoacidotic episodes are typically triggered by infection, fasting, or physical stress rather than occurring at random. Because both parents must carry a mutated copy of the gene for a child to be affected, and because the condition requires a specific metabolic trigger to become apparent, it remains extraordinarily rare, with only fifty to sixty cases reported worldwide.