What is Beta-Ketothiolase Deficiency? Beta-ketothiolase deficiency is an inherited disorder that causes the body to be unable to break down certain substances. The condition is caused by harmful genetic changes (variants) in the ACAT1 gene. Individuals with beta-ketothiolase deficiency cannot break down one of the building blocks of protein (isoleucine). They are also unable to process a key source of energy (ketones) used by the body during times of fasting or illness. These deficiencies lead to a build-up of toxic substances in the body, which cause the symptoms of the disease. The symptoms of beta-ketothiolase deficiency appear in the first decade of life, typically before the age of two. The first symptoms include vomiting, difficulty breathing, lack of energy, confusion, and may include seizures. The symptoms often appear quickly and are known as a "ketoacidotic attacks." These episodes, or crises, may be triggered by illness, infection, periods of fasting, or eating more protein-rich foods. If unrecognized and untreated with a special diet, the episodes can rapidly progress to coma and even death. Some individuals who survive one or more episodes may experience developmental delays. How common is Beta-Ketothiolase Deficiency? The incidence of beta-ketothiolase deficiency is estimated to be between 1 in 100,000 to 1 in 230,000. How is Beta-Ketothiolase Deficiency treated? There is no cure for beta-ketothiolase deficiency. Individuals with beta-ketothiolase deficiency need a special diet that is low in proteins and high-fat foods. Individuals also need to eat frequently and avoid fasting. Some individuals may need to supplement with carnitine. Individuals with beta-ketothiolase deficiency need close monitoring by a physician during illness. Symptoms such as vomiting, diarrhea, and illness with a fever require prompt treatment. What is the prognosis for an individual with Beta-Ketothiolase Deficiency? Without early diagnosis and treatment, beta-ketothiolase deficiency can be fatal. With early treatment, however, ketoacidotic attacks can be avoided, leading to improved growth, development, and intellectual ability. Despite treatment, some individuals may have developmental delays. Other names forbeta-ketothiolase deficiency 2-methyl-3-hydroxybutyricacidemia 3-alpha-oxothiolase deficiency 3-ketothiolase deficiency Alpha-methylacetoacetic aciduria MAT deficiency Methylacetoacetyl-coenzyme A thiolase deficiency T2 deficiency References Abdelkreem et al., 2019, Hum Mutat., 40(10):1641-1663, PMID: 31268215 Fukao et al., 2019, J Hum Genet., 64(2):99-111, PMID: 30393371 Gregg et al., 2021, Genet Med., 23(10):1793-1806, PMID: 34285390 Grunert et al., 2020, Orphanet J Rare Dis., 15(1):106, PMID: 32345314 OMIM: Online Mendelian Inheritance in Man, OMIM [203750], 2021, https://www.omim.org/entry/203750