Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. With the widespread use of tandem mass spectrometry for analysis of the. Combined malonic and methylmalonic aciduria, acsf3, mtfasii, metabolic flexibility, brain energy metabolism. This guideline is designed primarily as an educational resource for clinicians to help them provide quality medical care it should not be considered inclusive of all proper procedures and tests or exclusive of other pr ocedures and tests that are reasonably directed to obtaining the same results. The patient, 6 years old at the time of the report, was born at 34 weeks gestation to nonconsanguineous parents. Though rare, the symptoms of the disorder, which may include vomiting, seizures, heart disease, low blood sugar, delayed development, and retardation, can be serious, especially in infants.
An algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a. Brain metabolism and neurological symptoms in combined. Combined malonic and methylmalonic aciduria cmamma new york clients tests displaying the status new york approved. The result is a buildup of a substance called methylmalonic acid in the blood. Combined malonic and methylmalonic aciduria conditions. Expired lifetime application number us459288a inventor edgar c britton monroe ezra. Recently, combined malonic and methylmalonic aciduria cmamma has been shown to be caused by mutations in a putative methylmalonyl coa and malonyl coa synthetase acsf3. More commonly, malonic aciduria presents during infancy or later childhood with developmental delay, seizures, vomiting, failure to thrive, hypotonia, hypoglycemia, metabolic acidosis, and cardiomyopathy. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although. Proteomic and biochemical studies of lysine malonylation. Children with cmamma can suffer from developmental delays and a failure to gain weight and grow failure to thrive. Malonic acid, also called propanedioic acid, ho 2 cch 2 co 2 h, a dibasic organic acid whose diethyl ester is used in syntheses of vitamins b 1 and b 6, barbiturates, and numerous other valuable compounds malonic acid itself is rather unstable and has few applications.
Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Malonic ester synthesis is a synthetic procedure used to convert a compound that has the general structural formula 1 into a carboxylic acid that has the general structural formula 2. These autosomal recessive disorders result from deficient activity of methylmalonyl. An action act sheet is available for this condition that describes the shortterm actions a health professional should follow when an infant has a positive newborn screening result. This could lead to the succinic aciduria, and possibly oxoglutaric aciduria and aconitic aciduria. She had microcephaly, generalized hypotonia, brisk stretch reflexes, extensor. Pdf a rare case of malonic aciduria diagnosed by newborn. Newborn screening act sheet elevated c3dc acylcarnitine. Malonic aciduria genetic alliance information about early signs, followup testing. Ijns free fulltext a rare case of malonic aciduria. Malonic ester is a reagent specifically used in a reaction which converts alkyl halides to carboxylic acids called the malonic ester synthesis. Ethyl malonic aciduria encephalopathy with respiratory.
This topic gives an overview of the clinical presentation, diagnosis, and management of organic acidemias. Methylmalonic acidemia is an autosomal recessive disorder of amino acid metabolism, involving a defect in the conversion of methylmalonylcoenzyme a coa to succinylcoa. Malonic aciduria genetic alliance information about early signs, followup testing, treatment, accessing care, and expected outcomes. Malonic acid itself is rather unstable and has few applications. Longterm outcome and effects of expanded newborn screening using tandem mass spectrometry, j. Malonic definition and meaning collins english dictionary.
Ethyl malonic aciduria encephalopathy is a syndrome. Ethyl malonic aciduria encephalopathy with respiratory failure and nephrotic syndrome rare presentation authors. Its calcium salt occurs in beetroot, but the acid itself is u. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental delay, excessive tiredness lethargy, an enlarged. Newborn screening act sheet elevated c40h acylcarnitine. Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. A simple, rapid and sensitive method for the simultaneous determination of mma, 3mova, 2h3mb and 4mova has been developed and validated on hilicesims 2 without. Combined malonic and methylmalonic aciduria cmamma is an inherited condition in which certain chemicals accumulate in the blood and urine of affected individuals. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in.
Almost all affected children have delayed development. Combined malonic and methylmalonic aciduria due to acsf3. Their reactions with bases, called neutralizations, are accompanied by the evolution of substantial amounts of heat. Abstract ethyl malonic aciduria encephalopathy is a syndrome characterised by relapsing petechiae and progressive neurodegenerative symptoms and signs. The signs and symptoms of this disorder typically appear in early childhood. Gene identification and outcome study the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Succinic aciduria has also been reported in malonylcoa decarboxyl ase deficiency in which malonic acid accumulates 2. Malonic acids production and use as an intermediate in manufacture of barbituates and pharmaceuticals1 may result in its release to the environment through various waste streamssrc. Here, we suggest a novel hypothesis on the possible pathophysiological mechanism responsible for the development of neurological symptoms in the longrun. Methylmalonic acidemia can be caused by an inherited deficiency of methylmalonylcoa mutase, an adenosylcobalaminrequiring enzyme that converts lmethylmalonylcoa to succinylcoa figure 975, or in the metabolic pathway that catalyzes the biosynthesis of adenosylcobalamin from vitamin b 12 figure 978 and table 972.
Click on the link to view a sample search on this topic. Methylmalonic aciduria due to methylmalonylcoa mutase deficiency. The defining metabolic abnormality is the excretion of large amounts of ethyl malonic acid in the urine. Malonic acid, ho2cch2co2h, a dibasic organic acid whose diethyl ester is used in syntheses of vitamins b1 and b6, barbiturates, and numerous other valuable compounds. Methods and results we identified two probands with a nonclassical cmamma variant through the quebec newborn urine screening program. A new case of malonic aciduria with a presymptomatic diagnosis and an early treatment. Combined malonic and methylmalonic aciduria cmamma is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. Malonic acid malonic acid is a c3dicarboxylic acid currently used as an intermediate in the synthesis of numerous flavorsfragrances and pharmaceuticals. In its purified form, malonic acid is a white, crystalline substance, watersoluble and easily decomposed by heat. All structured data from the file and property namespaces is available under the creative commons cc0 license. Pubmed is a searchable database of medical literature and lists journal articles that discuss combined malonic and methylmalonic aciduria. A rare case of malonic aciduria diagnosed by newborn. Practical management of organic acidemias ios press.
This enzyme breaks down malonylcoa a fatty acid precursor and a fatty acid oxidation blocker into acetylcoa and carbon dioxide. Ethyl malonic aciduria encephalopathy is a syndrome characterised by relapsing petechiae and progressive neurodegenerative symptoms and signs. Malonic acid is a classic inhibitor of the citric acid cycle at the succinic acid dehydro genasc step. Pdf malonic aciduria is a rare autosomal recessive organic acid disorder. Methylmalonic acidemia genetics home reference nih. They react in this way with all bases, both organic for example, the amines and inorganic. Diverse symptoms are observed among the malonic aciduria patients, including delayed development, seizures, diarrhea, vomiting, low blood sugar hypoglycemia, and cardiomyopathy 22 it appears that inhibition of fatty acid catabolism caused by high level of malonylcoa is at least. Files are available under licenses specified on their description page. A white crystalline dicarboxylic acid, c3h4o4, that is a strong irritant and is used in making barbiturates. Mar 16, 2015 recently, combined malonic and methylmalonic aciduria cmamma has been shown to be caused by mutations in a putative methylmalonyl coa and malonyl coa synthetase acsf3. Succinic aciduria has also been reported in malonylcoa decarboxyl ase deficiency in which malonic. Novel hilicesims method for urinary profiling of msud and. Jan 17, 2012 access to this database is free of charge. Chemically, it is an organic dicarboxylic acid with a methylene group separating the two carbonyl moieties.
The patient, 6 years old at the time of the report, was born at. Over a 5 month period, the dog developed neurologic signs compatible with disease of the central nervous system with predominant diffuse cerebral and right lateralizing brainstem deficits. Malonic acid definition of malonic acid by the free dictionary. Signs and symptoms of this disorder typically appear in early childhood and include delayed development, hypotonia, seizures, diarrhea, vomiting, cardiomyopathy, and hypoglycemia.
Combined malonic and methylmalonic aciduria genetic and. Important organic acidurias see table 1 include propionic acidurias pa, methyl malonic acidurias mma, branched chain organic acidurias which includes isovaleric aciduria, glutaric aciduria type i, multiple carboxylase deficiency which is due to deficiency of 4 biotin dependent enzymes etc. With the widespread use of tandem mass spectrometry for analysis of the amino acidacylcarnitine profile on dried blood spots for newborn screening nbs, this condition can be readily diagnosed and can be included in the organic acid screen in nbs programs. Its calcium salt occurs in beetroot, but the acid itself is usually prepared by hydrolyzing diethyl malonate. People with cmamma can have a wide variety of symptoms. Act sheets were developed by experts in collaboration with the american college of medical genetics. Combined malonic and methylmalonic aciduria cmamma. While capable of being used in a wider variety of applications, demand has been held back by malonic acids high cost and environmentally hazardous production process. Malonic aciduria is a rare autosomal recessive organic acid disorder. Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin cbl. Methylmalonic acidemia an overview sciencedirect topics. The diethyl ester of this chemical is used chiefly as an intermediate in the synthesis of barbiturates. Jan 26, 2010 an 18monthold girl presented with recurrent episodes of encephalopathy, starting from the third postnatal day, and delayed development.
Methylmalonic acidemia mma or methylmalonic aciduria, simply, is the elevation of methylmalonic acid in the blood andor the urine generally it is seen in both. Combined malonic and methylmalonic aciduria due to acsf3 deficiency, termed non. Malonic acid is emitted to the atmosphere in gasoline engine emissions2, tobacco smoke3 and combustion of wood4. Isolated methylmalonic aciduria is found in patients with mutations in the mut gene causing partial, mut, or complete, mut 0, enzyme deficiency. Malonylcoa decarboxylase deficiency genetic and rare. Among these disorders, methyl malonic aciduria, propionic aciduria, maple syrup urine disease and isovaleric aciduria are sometimes referred to as classical organic acidurias. Malonic acid definition of malonic acid by medical dictionary. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental. In most publications, affected patients were identified during the investigation of various complaints.
Novel hilicesims method for urinary profiling of msud. Carboxylic acids donate hydrogen ions if a base is present to accept them. The group ch 2 co 2 h in 2 is contributed by a malonic ester, hence the term malonic ester synthesis. Aug 26, 2014 malonic acidemia also known as malonylcoenzyme a decarboxylase deficiency is an inherited disorder that prevents the body from converting certain fats to energy. International journal of neonatal screening case report a rare case of malonic aciduria diagnosed by newborn screening in qatar mamatha ramaswamy 1, victor anthony skrinska 1, ghassan abdoh 2, laila mahmoud ahmed 3, rola fayez mitri 1 and ravi joshi 1 1 metabolic laboratory, department of pathology and laboratory medicine, hamad medical corporation, p.
The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening. Pubmed is a searchable database of medical literature and lists journal articles that discuss malonylcoa decarboxylase deficiency. Dec 26, 2017 methylmalonic acidemia is an autosomal recessive disorder of amino acid metabolism, involving a defect in the conversion of methylmalonylcoenzyme a coa to succinylcoa. Methylmalonic and malonic aciduria in a dog with progressive. Dec 01, 2006 access to this database is free of charge. A 12 week old female labrador retriever dog with signs of progressive diffuse degeneration of the brain and spinal cord was found to have methlymalonic and malonic aciduria. Combined malonic and methylmalonic aciduria due to acsf3 mutations. Malonic acidemia also known as malonylcoenzyme a decarboxylase deficiency is an inherited disorder that prevents the body from converting certain fats to energy. Malonylcoa decarboxylase deficiency is inherited in an autosomal recessive pattern. The clinical significance of combined malonic and methylmalonic aciduria due to acsf3 deficiency cmamma is controversial. Malonylcoa decarboxylase deficiency mcd, is an autosomalrecessive metabolic disorder caused by a genetic mutation that disrupts the activity of malonylcoa decarboxylase.
This means that the defective gene is located on an autosome chromosome 16 is an autosome, and two copies of the defective gene one inherited from each parent are required to be born with the disorder. Methylmalonic and propionic aciduria pa are the most frequent forms of branched. Unusually high levels of malonic acid in the urine is often an indication of a genetic disorder known as malonic aciduria. Methylmalonic acidemia is a disorder in which the body cannot break down certain proteins and fats. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated. Levtova a, waters pj, buhas d, levesque s, aurayblais c, clarke jtr, laframboise r, maranda b, mitchell ga, brunelguitton c, et al. Malonic acidemia mal malonylcoa decarboxylase deficiency is a condition that prevents the body from converting certain fats to energy. While also a cause of elevated mma, the finding of elevated malonic acid in urine organic acid, and as evidenced on plasma acylcarnitine profile, is a distinguishing feature.
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