Beta ketothiolase deficiency is an inherited disorder in which the body cannot effectively process the amino acid isoleucine or ketones. Beta ketothiolase deficiency genetic and rare diseases nih. Beta ketothiolase deficiency disease definition a rare, genetic organic aciduria affecting ketone body metabolism and the catabolism of isoleucine and characterized by intermittent ketoacidotic episodes associated with vomiting, dyspnea, tachypnoea, hypotonia, lethargy and coma, with an onset during infancy and usually ceasing by adolescence. Bkt is a condition in which the body cannot properly process a particular amino acid a building block of proteins or the products of fat breakdown. The deficiency of aat1 means that the body is unable to properly break down fats and proteins causing a build up of compounds which become toxic and damage the tissues and organs. Betaketothiolase deficiency an overview sciencedirect. Betaketothiolase deficiency genetics home reference nih. Early signs symptoms can begin in infancy and males have more severe symptoms. Hadhb is a subunit of the mitochondrial trifunctional protein and has thiolase activity. Betaketothiolase deficiency is also known by other names including t2 deficiency, mitochondrial acetoacetylcoa thiolase deficiency, 3oxothiolase deficiency, 3ketothiolase deficiency, and 2methyl3hydroxybutyric acidemia. Mitochondrial acetoacetylcoa thiolase deficiency is a disease that varies in age at onset and severity.
Betaketothiolase deficiency is also known by other names. Metabolic encephalopathy in beta ketothiolase deficiency. Mitochondrial acetoacetylcoa thiolase deficiency 0317. Betaketothiolase deficiency is a rare inborn errors of metabolism iem affecting the. Imaging findings relating to this entity have rarely been reported. Beta ketothiolase deficiency is inherited in an autosomal recessive manner. Beta ketothiolase deficiency bktd is an autosomal recessive disease caused by a defect of mitochondrial acetoacetylcoa thiolase. Betaketothiolase deficiency is an inherited disorder of ketone body metabolism and.
So far, about 5 cases with betaketothiolase deficiency have been reported in the literature with similar symptoms to our case such as intermittent. Betaketothiolase deficiency is a rare inborn errors of metabolism iem affecting the catabolism of isoleucine, characterized by severe ketoacidosis in children of 6 to 24 months old. Gas liquid chromatography of her urine revealed excretion of large amounts of. This disorder is characterized by normal early development followed by a progressive loss of mental and motor skills. The signs and symptoms of this condition typically appear between the ages of 6 months and 24 months. The organic acid disorders tested in newborn screening include methylmalonic acidemia mma, propionic acidemia pa, isovaleric acidemia iva, 3methylcrotonylcoenzyme a carboxylase 3mcc deficiency, multiple carboxylase deficiency mcd, glutaric aciduria type 1 and 2 ga1 and ga2, betaketothiolase bkt deficiency, and 3hydroxy3methylglutariccoenzyme a lyase. Betaketothiolase t2 deficiency is an inherited disease of isoleucine and ketone body metabolism caused by mutations in the acat1 gene. Developed by the american college of medical genetics and genomics and the national coordinating center for. However, several challenges in the diagnosis of betaketothiolase deficiency have been encountered. Betaketothiolase deficiency is a defect in the catabolism of the branchedchain amino acid isoleucine. Beta ketothiolase deficiency is a defect in the catabolism of the branchedchain amino acid isoleucine. This disorder also impairs the bodys ability to process ketones, which are molecules produced during the breakdown of fats.
Affected children experience episodes of vomiting, dehydration, difficulty breathing, lethargy, and. The specific term mitochondrial acetoacetylcoa thiolase deficiency is preferable to beta ketothiolase deficiency. The following terms are synonyms for beta ketothiolase deficiency. Betaketothiolase deficiency an overview sciencedirect topics. Bkt is a rare inherited genetic disease that does not allow a baby to break down an amino acid a building block of protein called isoleucine. So far, about 5 cases with betaketothiolase deficiency have been reported in the literature with similar symptoms to our case such as intermittent ketoacidosis attacks in some patients and neurological symptoms confusion, lethargy, decrease of consciousness level, movement disorder, and coma in some others 6.
Isoleucine is found in foods that contain protein, including breast milk and infant formula. Beta ketothiolase deficiency mitochondrial acetoacetylcoa thiolase, mat or t2 deficiency is a rare autosomal recessive disorder of isoleucine and ketone body metabolism due to acetylcoa acetyltransferase1 acat1 gene. Metabolic encephalopathy in betaketothiolase deficiency. Between 2005 and 2016, a total of 41 patients with t2 deficiency were identified at a medical center in northern. Jun 28, 2017 beta ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block amino acid called isoleucine. Diagnostic flow chart for betaketothiolase t2 deficiency. Diagnostic flow chart for beta ketothiolase t2 deficiency. Beta ketothiolase t2 deficiency is an inherited disease of isoleucine and ketone body metabolism caused by mutations in the acat1 gene. Ketothiolase deficiency is a defect of mitochondrial acetoacetylcoa thiolase t2 involving ketone body metabolism and isoleucine catabolism. Pdf characterization and outcome of 41 patients with beta.
Betaketothiolase deficiency or 2methylacetoacetyl coa thiolase deficiency is a rare hereditary and treatable neurometabolic disorder with various clinical manifestations. What happens to protein and fats in a child with bkt deficiency. Betaketothiolase deficiency is a rare inborn errors of metabolism iem affecting the catabolism of isoleucine. In a german boy with 3ketothiolase deficiency, born of nonconsanguineous parents, fukao et al. Beta ketothiolase deficiency is a rare inborn errors of metabolism iem affecting the catabolism of isoleucine, characterized by severe ketoacidosis in children of 6 to 24 months old. In order for the body to use protein from the food we eat, it is broken down into smaller parts called amino acids.
Betaketothiolase deficiency new york clients tests displaying the status new york approved. It is treatable, but can cause lifethreatening illness. A prompt diagnosis is of paramount importance as the metabolic decompensation can be effectively reverted by glucose infusion and health outcomes are improved on. Beta ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown. Despite thereported missed cases, screening programs have successfully identified an increasing number of patients with beta ketothiolase deficiency. Trifunctional enzyme subunit beta, mitochondrial tp beta also known as 3ketoacylcoa thiolase, acetylcoa acyltransferase, or beta ketothiolase is an enzyme that in humans is encoded by the hadhb gene. Affected children experience episodes of vomiting, dehydration, difficulty in breathing, unexplained lethargy and seizures. Coa thiolase deficiency is an autosomal recessive disorder of isoleucine catabolism.
Signs and symptoms typically appear between the ages of 6 and 24 months. This was apparently the first definition of a mutant acat allele. The following terms are synonyms for betaketothiolase deficiency. Trifunctional enzyme subunit beta, mitochondrial tpbeta also known as 3ketoacylcoa thiolase, acetylcoa acyltransferase, or betaketothiolase is an enzyme that in humans is encoded by the hadhb gene hadhb is a subunit of the mitochondrial trifunctional protein and has thiolase activity. Betaketothiolase deficiency as a treatable neurometabolic. Each pregnancy between carrier parents i has a 25% chance of producing a child affected with beta ketothiolase. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condtion. Despite the reported missed cases, screening programs have successfully identified an increasing number of patients with beta ketothiolase deficiency.
The signs and symptoms of beta ketothiolase deficiency appear between the ages of 6 24 months, and in some rare cases up to 37 years. The human t2 cdna has a 1281base open reading frame, and its gene. Beta ketothiolase deficiency bkt is a metabolic disorder. Betaketothiolase definition of betaketothiolase by. Frequency of decompensation attacks decreases with age and decompensation is uncommon after the age of 10 years. Mild form of betaketothiolase deficiency mitochondrial acetoacetylcoa thiolase deficiency in two japanese siblings.
So far, about 5 cases with beta ketothiolase deficiency have been reported in the literature with similar symptoms to our case such as intermittent. Beginning in 2014, we carried out newborn screening by tandem mass spectrometry msms followed by nextgeneration sequencing ngs and identified two infants with bktd among 203,750 newborns born in jiangsu. A patient was investigated who had the ketotic hyperglycinemia syndrome with normal propionate and methyimalonate metabolism, but with a markedly decreased ability to catabolize isoleucine. Enable javascript to view the expandcollapse boxes. Parent fact sheet betaketothiolase deficiency bkt bay. However, the name beta ketothiolase deficiency is exclusively used for the defect of mitochondrial acetoacetylcoa thiolase ec 2. Betaketothiolase deficiency is an inherited disorder in which the body cannot effectively process the amino acid isoleucine or ketones.
Newborn creening fact heet nd newborn screening program. This booklet contains general information about ketone utilization disorder, previously called betaketothiolase deficiency. Ketone utilization disorder betaketothiolase deficiency organic. This disorder affects ketone body metabolism and isoleucine catabolism. Betaketothiolase deficiency bkt is a metabolic disorder. Betaketothiolase deficiency is caused by mutations stable and hereditary changes in the acat1 gene that encodes this enzymatic protein.
Coa thiolase deficiency is an autosomal recessive disorder of isoleucine catabolism and ketone body metabolism that is characterized by increased urinary excretion of 2. The signs and symptoms of betaketothiolase deficiency typically. Beta ketothiolase deficiency kansas department of health. Bkd beta keto 4 of 4 may 2008 1 ketone utilization disorder. Betaketothiolase deficiency disease definition a rare, genetic organic aciduria affecting ketone body metabolism and the catabolism of isoleucine and characterized by intermittent ketoacidotic episodes associated with vomiting, dyspnea, tachypnoea, hypotonia, lethargy and coma, with an onset during infancy and usually ceasing by adolescence.
Beginning in 2014, we carried out newborn screening by tandem mass spectrometry msms followed by nextgeneration sequencing ngs and identified two infants with bktd among 203,750 newborns born in jiangsu province, china. Beta ketothiolase deficiency bkt baytakeytoethigholace defishensee what is bkt. This condition also impairs the bodys ability to process ketones, which are molecules produced during the breakdown of fats. The specific term mitochondrial acetoacetylcoa thiolase deficiency is preferable to betaketothiolase deficiency.
Ketothiolase deficiency is a deficiency of mitochondrial acetoacetylcoa thiolase t2. Two infants with betaketothiolase deficiency identified. Nmrbased urinalysis for betaketothiolase deficiency. Disease name beta ketothiolase deficiency alternate names alphamethylacetoacetic aciduria, 2methyl3hydroxybutyric academi, mitochondrial acetoacetylcoa thiolase deficiency, mat deficiency, t2 deficiency, 3oxothiolase deficiency, 3 ketothiolase deficiency, 3ktd deficiency acronym bkt disease classification organic acid disorder. Betaketothiolase deficiency mitochondrial acetoacetylcoa thiolase, mat. Beta ketothiolase deficiency bkt is an organic acid disorder that results from an inability to process the amino acid isoleucine. Cause an enzyme needed to break down protein and fats from food is not working correctly. Two infants with betaketothiolase deficiency identified by. Bkt deficiency is a treatable disorder that affects the way the body processes protein and fats. Betaketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown. The clinical phenotype and outcome of mitochondrial acetoacetylcoa thiolase deficiency. Pdf betaketothiolase deficiency is an inherited disorder of ketone body metabolism and isoleucine catabolism. Special enzymes then make changes to the amino acids so the body can use them bkd occurs when an enzyme, called mitochondrial acetoacetylcoa thiolase mat, is either missing or not working properly.
The typical age of onset for this disorder is between 6 months and 24 months. A final diagnosis of betaketothiolase deficiency requires an enzymatic assay andor a molecular analysis, but some caveats must be considered. A final diagnosis of beta ketothiolase deficiency requires an enzymatic assay andor a molecular analysis, but some caveats must be considered. In a german boy with 3 ketothiolase deficiency, born of nonconsanguineous parents, fukao et al. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. Despite the reported missed cases, screening programs have successfully identified an increasing number of. Betaketothiolase deficiency is a defect of mitochondrial acetoacetylcoa thiolase t2 involving ketone. Beta ketothiolase deficiency or 2methylacetoacetyl coa thiolase deficiency is a rare hereditary and treatable neurometabolic disorder with various clinical manifestations. These episodes which are called ketoacidotic attacks can lead to coma. Request pdf nmrbased urinalysis for betaketothiolase deficiency background.
Betaketothiolase deficiency is an inherited disorder in which the body. An equal opportunity employer mfd disease name betaketothiolase deficiency alternate names alphamethylacetoacetic aciduria, 2methyl3hydroxybutyric academi, mitochondrial acetoacetylcoa thiolase deficiency, mat deficiency, t2. Betaketothiolase deficiency online mendelian inheritance in man omim 203750 is an autosomal recessive disease caused by a defect of mitochondrial acetoacetylcoa thiolase t2. Fasting for too long may decrease the ratio, and glucose infusion reduces ffa faster. Clinical outcome varies widely, with a few patients suffering severe psychomotor retardation or death as a result of their initial attack and others. The acmg act sheets and their accompanying algorithms are a great resources for health care providers looking for information on genetic conditions identified through newborn screening and beyond to help inform clinical decision making. Betaketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block amino acid called isoleucine.
However, the name betaketothiolase deficiency is exclusively used for the defect of mitochondrial acetoacetylcoa thiolase ec 2. Parent fact sheet betaketothiolase deficiency bkt bayta. Thin layer chromatography of dinitrophenylhydrazones of urinary. Both males and females can have lack of energy, poor feeding, muscle weakness, and seizures. So far, about 5 cases with beta ketothiolase deficiency have been reported in the literature with similar symptoms to our case such as intermittent ketoacidosis attacks in some patients and neurological symptoms confusion, lethargy, decrease of consciousness level, movement disorder, and coma in some others 6. Betaketothiolase deficiency as a cause of the ketotic. Beta ketothiolase deficiency is also known by other names including t2 deficiency, mitochondrial acetoacetylcoa thiolase deficiency, 3oxothiolase deficiency, 3 ketothiolase deficiency, and 2methyl3hydroxybutyric acidemia. Bkt deficiency is a genetic disorder of autosomal recessive inheritance, which means that parents are usually carriers of a acat1 gene mutation without presenting symptoms. Betaketothiolase deficiency bktd is an autosomal recessive disease caused by a defect of mitochondrial acetoacetylcoa thiolase. Beta ketothiolase deficiency genetic and rare diseases. Pdf characterization and outcome of 41 patients with.
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