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. Use of a range of 3ketoacylcoa substrates showed that the other 3ketothiolase isoenzymes were normal in each case. Compilation of information, articles, and links to support. Betaketothiolase deficiency how is betaketothiolase. It results from biallelic pathogenic variants in the acat1 gene, encoding mitochondrial beta ketothiolase. Nmrbased urinalysis for betaketothiolase deficiency.
Pdf first report of 3oxothiolase deficiency in iran. Both patients had episodic ketosis and metabolic acidosis. Betaketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block amino acid called isoleucine. Because of the high rate of consanguineous marriages in iran, physicians should consider the 3oxothiolase deficiency in the differential diagnosis of any patient with intractable vomiting and severe metabolic acidosis. Mri of pallidal involvement in betaketothiolase deficiency. Betaketothiolase deficiency is an inherited disorder of ketone body metabolism and. Betaketothiolase deficiency is a defect of mitochondrial acetoacetylcoa thiolase t2 involving ketone. Betaketothiolase deficiency genetics home reference nih. It is clinically characterized by intermittent ketoacidotic episodes, with no.
However, several challenges in the diagnosis of betaketothiolase deficiency have been encountered. Mckat newborn screening coding and terminology guide. 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. Genedx 207 perry parkway gaithersburg, md 20877 toll free. Mct1d in their index patient, a girl of consanguineous syrian descent with recurrent, severe acidosis, van hasselt et al. This condition also impairs the bodys ability to process ketones, which are molecules produced during the breakdown of fats.
Diagnostic flow chart for betaketothiolase t2 deficiency. Mitochondrial cytopathy see this topic due to the autosomal recessive transmission of a mutation in the acat1 gene 11q22. Betaketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the. The signs and symptoms of this condition typically appear between the ages of 6 months and 24 months.
Mediumchain ketoacylcoa thiolase deficiency mcat is a condition in which the body is unable to breakdown certain fats. We report two cases of beta ketothiolase deficiency presenting with acute. This disorder can lead to breathing problems, convulsions, coma, and death. This disorder also impairs the bodys ability to process ketones, which are molecules produced during the breakdown of fats. In a german boy with 3 ketothiolase deficiency, born of nonconsanguineous parents, fukao et al. Imaging findings relating to this entity have rarely been reported. 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. Without treatment, patients with classic pku have no symptoms at birth, but usually develop them by 6 months of age. Homocysteine accumulates and dimerizes to form the disulfide homocystine, which is excreted in the urine. Beta ketothiolase deficiency bkt is an organic acid disorder that results from an inability to process the amino acid isoleucine. The signs and symptoms of scot deficiency typically appear within the first few years of life. 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 deficiency hmgcoa. Beta ketothiolase mitochondrial acetoacetylcoa thiolase.
Apr 20, 2011 mediumchain ketoacylcoa thiolase deficiency is a disorder associated with vomiting, dehydration, metabolic acidosis, liver dysfunction, and rhabdomyolysis. Act sheet for elevated c5oh acylcarnitine acmg pdf document 400. In contrast, no coatransferase activity was present in any of the tissues from patient c table i. This definition appears rarely and is found in the following acronym finder categories. The human t2 cdna has a 1281base open reading frame, and its gene spans 27 kb and contains 12 exons. Mutations in this gene reduce or eliminate the activity of the enzyme mitochondrial acetoacetylcoa thiolase. Coatransferase activity was highest in the brain with decreasing values in the kidney and muscle tissues. Betaketothiolase deficiency an overview sciencedirect topics. Two patients have been studied in whom the activity of the short chainlengthspecific mitochondrial 3 ketothiolase was found to be deficient. This disorder is characterized by normal early development followed by a progressive loss of mental and motor skills. Betaketothiolase deficiency bkt arkansas childrens. Mim 203 750 deficit in mitochondrial acetylcoa thiolase, deficiency in t2, alphamethylacetoacetic aciduria extremely rare.
Patients with bkt deficiency should not be kept without food for extended periods of time. Betaketothiolase deficiency is an inherited disorder in which the body cannot effectively process the amino acid isoleucine or ketones. Betaketothiolase deficiency presenting with metabolic. Thiolases are a family of evolutionarily related enzymes. Beta ketothiolase mitochondrial acetoacetylcoa thiolase deficiency is a genetic disorder characterized by impaired isoleucine catabolism and ketone body utilization that predisposes to episodic ketoacidosis. Two patients have been studied in whom the activity of the short chainlengthspecific mitochondrial 3ketothiolase was found to be deficient. Beta ketothiolase deficiency genetic and rare diseases. One patient had substantial evidence of damage to the central. The optimal time to determine genetic risk, clarify carrier status of parents, and discuss the availability of prenatal testing is before pregnancy.
In a german boy with 3ketothiolase deficiency, born of nonconsanguineous parents, fukao et al. Increasing the amount of homogenate protein in the re. Betaketothiolase deficiency is an autosomal recessive disorder that causes the. Diagnostic flow chart for beta ketothiolase t2 deficiency. The specific term mitochondrial acetoacetylcoa thiolase deficiency is preferable to betaketothiolase deficiency. 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. Beta ketothiolase deficiency is an inherited disorder in which the body cannot effectively process the amino acid isoleucine or ketones.
Isoleucine is found in foods that contain protein, including breast milk and infant formula. This disorder is caused by an autosomal recessive deficiency of cystathionine betasynthase, which catalyzes cystathionine formation from homocysteine and serine. The following terms are synonyms for betaketothiolase deficiency. Betaketothiolase mitochondrial acetoacetylcoa thiolase deficiency is a genetic disorder characterized by impaired isoleucine catabolism and ketone body utilization that predisposes to episodic ketoacidosis. Use of a range of 3ketoacylcoa substrates showed that the other 3 ketothiolase isoenzymes were normal in each case. The function of this gene play an important role in ketone body metabolism and the diseases associated with this gene include the following. What happens to protein and fats in a child with bkt deficiency. Clinical characteristics with treatment by early introduction and maintenance of special diet, normal iq and development can be expected. Use of a range of 3ketoacylcoa substrates showed that the other 3. It is considered a fatty acid oxidation condition because people affected by mcat are unable to change some of the fats they eat.
Beta ketothiolase deficiency kansas department of health. The typical age of onset for this disorder is between 6 months and 24 months. The cause of mediumchain ketoacylcoa thiolase deficiency is unknown. The following terms are synonyms for beta ketothiolase deficiency. Coa thiolase deficiency is an autosomal recessive disorder of isoleucine catabolism. This was apparently the first definition of a mutant acat allele.
The clinical picture was mild, as only during periods with infections does metabolic acidosis develop and clinical abnormalities. 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. The signs and symptoms of scot deficiency typically appear within the first few years of. The diagnosis of b ketothiolase deficiency is confirmed by finding a specific urine organic acid and plasma acylcarnitine profiles.
However, the name beta ketothiolase deficiency is exclusively used for the defect of mitochondrial acetoacetylcoa thiolase ec 2. Psychomotor development of both patients was normal. 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 24months old. There is considerable heterogeneity in clinical features, while a unique presentation is the attacks of massive. Mediumchain ketoacylcoa thiolase deficiency is extremely rare. Betaketothiolase deficiency an overview sciencedirect. The 3oxothiolase deficiency is a rare disorder involving ketone body metabolism. One patient had substantial evidence of damage to the central nervous system. It results from biallelic pathogenic variants in the acat1 gene, encoding mitochondrial betaketothiolase. Ketothiolase deficiency is a defect of mitochondrial acetoacetylcoa thiolase t2 involving ketone body metabolism and isoleucine catabolism. Alternate names alphamethylacetoacetic aciduria, 2methyl3hydroxybutyric academi, mitochondrial acetoacetylcoa thiolase deficiency, mat deficiency, t2 deficiency, 3oxothiolase deficiency, 3 ketothiolase deficiency, 3ktd deficiency.
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, beta ketothiolase bkt deficiency, and 3hydroxy3methylglutariccoenzyme a lyase deficiency hmgcoa. Betaketothiolase bkt deficiency is a rare autosomal recessive metabolic disorder, which causes episodic severe metabolic acidosis. Betaketothiolase deficiency in a family confirmed by in. All content on this website, including dictionary, thesaurus, literature, geography, and other reference data is for informational purposes only. Mutations in the acat1 gene cause beta ketothiolase deficiency. T2 hcy homocystinuria cystathionine beta synthase mcd multiple carboxylase holocarboxylase synthetase tfp trifunctional protein cbl a,b methylmalonic acidemia vitamin b12 disorders hmg 3hydroxy 3 methylglutaric aciduria 3hydrox 3. The enzymatic defect is the deficiency of mitochondrial acetoacetyl coa thiolase and the responsible gene is on chromosome 11q22. Dna molecular testing of acat1 gene may help also in confirming the diagnosis. Because remethylation is intact, some of the additional homocysteine is converted to methionine, which accumulates in the blood. Enable javascript to view the expandcollapse boxes. Alternate names alphamethylacetoacetic aciduria, 2methyl3hydroxybutyric academi, mitochondrial acetoacetylcoa thiolase deficiency, mat deficiency, t2 deficiency, 3oxothiolase deficiency, 3ketothiolase deficiency, 3. Affected children experience episodes of vomiting, dehydration, difficulty breathing, lethargy, and. 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. Middleton b, bartlett k, romanos a, gomez vazquez j, conde c, cannon ra, lipson m, sweetman l, nyhan wl.
Two different types of thiolase are found both in eukaryotes and in prokaryotes. Other deficiencies of circulating enzymes short description. The 4 disorders are methionine adenosyltransferase mat deficiency, glycinenmethyltransferase gnmt deficiency, sadenosylhomocysteine hydrolase sahh deficiency and adenosine kinase ak deficiency. Bketothiolase deficiency national guard health affairs. 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. We report a case of a 5yearold girl with bkt deficiency with isolated focal t2 hyperintensities involving the globi pallidi, which demonstrated. Betaketothiolase deficiency, ketoacidosis, ataxia telangiectasia and metabolic disorder. 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. 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. Betaketothiolase deficiency is a rare inborn errors of metabolism iem affecting the catabolism of isoleucine, characterized by severe ketoacidosis in children of 6 to 24months old.
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. Fasting for too long may decrease the ratio, and glucose infusion reduces ffa faster. Genetic disorders leading to hypoglycaemia longdom publishing. Betaketothiolase definition of betaketothiolase by.
However, the name betaketothiolase deficiency is exclusively used for the defect of mitochondrial acetoacetylcoa thiolase ec 2. Beta ketothiolase bkt deficiency is a rare autosomal recessive metabolic disorder, which causes episodic severe metabolic acidosis. Mediumchain ketoacylcoa thiolase deficiency is a disorder associated with vomiting, dehydration, metabolic acidosis, liver dysfunction, and rhabdomyolysis. Betaketothiolase deficiency is an inherited disorder in which the body cannot.