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Beta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. This condition also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats. Signs and symptoms typically appear between the ages of 6 and 24 months. Affected children experience intermittent episodes of ketoacidosis, characterized by vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and occasionally, seizures. In severe cases, these episodes can lead to coma. Metabolic stroke is another finding that has been increasingly reported in children with this condition. Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein- rich foods.
Beta ketothiolase deficiency is inherited in an autosomal recessive fashion and is caused by pathogenic variants (mutations) in the ACAT1 gene. Treatment involves managing acute crises with intravenous (IV) fluids, glucose, and electrolytes along with bicarbonate. Long-term management involves eating frequently, following a reduced-protein diet, avoidance of high-fat foods, and, in some cases, carnitine supplementation.
Source: GARD Last updated on 05-01-20
Couples who are at high risk for having a child with beta ketothiolase deficiency have several options that may be available either before a pregnancy or during a pregnancy. The optimal time to determine genetic risk, clarify carrier status of parents, and discuss the availability of prenatal testing is before pregnancy. Genetic counseling (which includes a discussion of potential risks to offspring as well as reproductive options) is recommended for individuals who are affected, are carriers, or are at risk of being carriers for genetic disorders.
Finding out the genetic status of the fetus during a pregnancy for pregnancies at high risk (i.e. those at 25% risk based on family history) is possible either by analyzing T2 activity (the defective enzyme in the disorder) or by detecting mutations in fetal DNA. These tests can be performed following either chorionic villus sampling (CVS) between approximately 10 and 12 weeks gestation, or amniocentesis usually between 15 and 18 weeks gestation. For couples seeking DNA analysis to identify whether the fetus has inherited specific disease-causing mutations, the mutations in an affected family member or in the carrier parents must be known before prenatal testing can be performed.
As an alternative to prenatal diagnosis during the pregnancy, preimplantation genetic diagnosis (PGD) may be available months before a pregnancy begins if the disease-causing mutations have been identified. Preimplantation diagnosis is done following in vitro fertilization (IVF) to diagnose a genetic disease in an embryo before it is introduced into the uterus. When doing PGD, laboratories can test a single cell from an embryo that is just days old. Besides testing for the specific disorder in question, PGD can also provide information about whether the embryo is male or female and whether it is carrying chromosomal abnormalities or rearrangements.
GeneTests lists the names of laboratories that are performing testing for beta ketothiolase deficiency. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional. To view the contact information for the clinical laboratories conducting testing (including prenatal diagnosis), click here. For a list of laboratories that offer PGD, click here.
Last updated on 05-01-20
The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
Last updated on 04-27-20
Akella RRD, Aoyama Y, Mori C, Lingappa L, Cariappa R, Fukao T. Metabolic encephalopathy in beta-ketothiolase deficiency: The first report from India. Brain Dev. Jun 2014; 36(6):537-40.
Last updated on 04-27-20
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