Methylmalonic acidemia is a disorder in which the body cannot break down certain proteins and fats. Mmaa is involved in the synthesis of adenosylcobalamin adocbl, a coenzyme for methylmalonylcoa mutase mut. Methylmalonic acidurias mma european registry and network for. Methylmalonic acidurias are biochemically characterized by an accumulation of methylmalonic acid in tissues and body fluids. What links here related changes upload file special pages permanent link page. Propionic acidemia prop, methylmalonic acidemia mut. Newborn screening for methylmalonic aciduria by tandem mass spectrometry. Methylmalonic acidemia diagnosis by laboratory methods.
Incorrect metabolism means your body might have too much or too little of a metabolite which can have detrimental impacts on. Please remove adblock adverts are the main source of revenue for dovemed. The result is a buildup of a substance called methylmalonic acid in. In one step of metabolism, vitamin b12 promotes the conversion of methylmalonyl coa a form of mma to succinyl coenzyme a. Mma is a substance produced in very small amounts in the body. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia.
Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid due to deficiency of methylmalonylcoa mutase mut or propionylcoa carboxylase pcc. Methylmalonic acidemia genetics home reference nih. Mma encompasses a heterogeneous group of disorders characterized by accumulation of methylmalonic acid and its by. The methylmalonic acid mma test may be used to help diagnose an early or mild vitamin b12 deficiency. Isolated methylmalonic acidemia aciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut.
The uphs marquette reference lab is a fully integrated, comprehensive provider of laboratory services to inpatients, outpatients, outreach clients and other community health care organizations across michigans upper peninsula. About 1 in 20 000 babies are born with methylmalonic acidemia each year in canada. Methylmalonic acidemia with homocystinuria is an inherited disorder in which the body is unable to properly process protein building blocks amino acids, certain fats lipids, and a waxy fatlike substance called cholesterol. Laboratory procedure manual centers for disease control.
Prevalence of 148,000161,000 has been reported for methylmalonic aciduria of all causes in north. Mma is characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat byproducts resulting in seizures, strokes, and chronic. The documents contained in this web site are presented for information purposes only. Carrier screening to help detect the risk of having a baby with a specific inherited disorder, such as cystic fibrosis. 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. Through clinical and scientific study, researchers have been able to elucidate the biochemistry and cell biology that underlies these two diseases. Elevated levels of methylmalonic acid mma result from inherited defects of enzymes involved in mma metabolism or inherited or acquired deficiencies. Testing for this disorder is often done as part of a newborn screening exam this test may also be done with other tests to check for a vitamin b12 deficiency. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid due to deficiency of methylmalonylcoa. Propionic and methylmalonic acidemia are recessive disorders of the metabolism of thr,val, ile, met, odd chain fatty acids, and cholesterol classic presentation is with shock, acidosis and hyperammonemia, neutropenia and thrombocytopenia it is diagnosed by urine organic acids methylcitrate or methylmalonic acid, plasma amino acids. We have investigated the value of oral metronidazole 1020 mgkg per day in five children with methylmalonic acidaemia mma and four with propionic acidaemia pa. Methylmalonic acidemia with homocystinuria orphanet.
Get a printable copy pdf file of the complete article 1. Vitamin b12unresponsive methylmalonic acidemia is an inborn error of vitamin b12. Nemch methylmalonic acidemia is one of the inborn errors capable of producing severe ketoacidosis. Pdf methylmalonic acidemia with emergency hypertension. It may be ordered by itself or along with a homocysteine test as a followup to a vitamin b12 test result that is in the lower end of the normal range. Newborn screening for methylmalonic aciduria by tandem. Methylmalonic acidemia mma is widely considered as an autosomal recessive.
Methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening. The use of metronidazole in management of methylmalonic.
Pdf merge combine pdf files free tool to merge pdf online. Started in 1995, this collection now contains 6767 interlinked topic pages divided into a tree of 31 specialty books and 732 chapters. Methylmalonic acidemia is a disorder, passed down through families, in which the body cannot break down certain proteins and fats. Methylmalonic acidemia mma is an organic acid disorder.
Review open access proposed guidelines for the diagnosis. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine. Insights into the molecular mechanisms of methylmalonic acidemia. Patients and their families work with nih researchers to advance research on methylmalonic acidemia duration. Methylmalonic acidemia nicklaus childrens hospital. Please note, for carriertargeted variant tests the approval status depends on whether the gene is in an approved. Methylmalonic acid mma is a substance produced in very small amounts and is necessary for human metabolism and energy production. Genetics of methylmalonic acidemia clinical presentation.
Methylmalonic acidemia, vitamin b12 responsive the british inherited metabolic disease group bimdg has published on its website guidelines for the emergency management of patients with inherited metabolic disorders. Methylmalonic acidemia, cobalamin c type, presenting with cutaneous manifestations. Propionic acidemia is caused by a defect in the enzyme propionylcoa carboxylase. In this way, it enters the krebs cycle, and is thus part of one of the anaplerotic.
The health care provider may order this test if there are signs of certain genetic disorders, such as methylmalonic acidemia. A metabolic disorder results when an enzyme responsible for the breakdown of our food is defective which results in compounds, also known as metabolites, accumulating in blood or urine. Methylmalonic acid mma conjugate base methylmalonate is a dicarboxylic acid that is a cmethylated derivative of malonate the coenzyme a linked form of methylmalonic acid, methylmalonylcoa, is converted into succinylcoa by methylmalonylcoa mutase, in a reaction that requires vitamin b 12 as a cofactor. Mouse model for methylmalonic acidemia, an inherited. Methylmalonic and propionic acidemia are two organic acidemias. Combined malonic and methylmalonic aciduria cmamma new york clients. 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. Serum methylmalonic acid mma measurement is used to evaluate individuals with signs. The range of methylmalonic acid in plasma or serum from healthy adults is 0.
Methylmalonic acid mma conjugate base methylmalonate is a dicarboxylic acid that is a. Here are the ones the management for an acute decompensation in children and adults with methylmalonic acidemia due to a. Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy lethargy. The methylmalonic acid test is a simple blood test. Methylmalonic acidemia can occur in individuals of all races and ethnicities, with an incidence in the united states of approximately 191,000 and a calculated carrier frequency of 1 in 151. Methylmalonic aciduria is caused by the deficient activity of methylmalonylcoa mutase mcm, a vitamin b12 dependent mitochondrial enzyme which is essential.
Matsui sm, mahoney mj, rosenberg le 1983 the natural history of the inherited methylmalonic acidemias. Enable javascript to view the expandcollapse boxes. Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. National human genome research institute 2,887 views. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. It shares some clinical and biochemical features with propionic acidemia because methylmalonyl coenzyme a coa is just one step beyond propionyl coa on the way to the formation of succinyl coa fig. Methylmalonic acidemia cbl a,b information for health professionals. Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. Methylmalonic acidemia adult metabolic diseases clinic. Methylmalonic acidemia mma describes a group of genetic, organic acid disorders in which the body is unable to breakdown certain proteins and fats, resulting in the buildup of methylmalonic acid in blood. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Once files have been uploaded to our system, change the order of your pdf documents.
Manual, which can be downloaded at downloadsfiles loincmanual. Gut bacteria have been implicated as an important source of propionate in children with inborn errors of propionate metabolism. Methylmalonic acidemia multimedia encyclopedia health. Methylmalonic acidemia diagnosis by laboratory methods fatemeh keyfi1, 2, saeed talebi3, abdolreza varasteh2, 4, 5 abstract methylmalonic acidemia mma is usually caused by a deficiency of the enzyme methylmalonylcoa mutase mcm, a defect in the transport or synthesis of its cofactor, adenosylcobalamin cbla, cblb, cblc, cblf, cbld. Methylmalonic acidemia with homocystinuria genetics home. Vitamin b12 unresponsive methylmalonic acidemia orphanet. Vitamin b12 responsive forms include cobalamin a cbla and cobalamin b cblb deficiencies. Patients present either shortly after birth with acute.
Proposed guidelines for the diagnosis and management of. They are caused by an inherited deficiency of the mitochondrial enzyme methylmalonylcoa mutase ec 5. Patients with methylmalonic acidemia with homocystinuria of all types can present with developmental delay, signs. Labcorp test details for methylmalonic acid, serum or plasma. Methylmalonic acidemia kansas department of health.
High levels of methylmalonic acid may indicate a vitamin b12 deficiency. Once you merge pdfs, you can send them directly to your email or download the file to our computer and view. Methylmalonic acidemia can be due to a defect in an enzyme methylmalonylcoa mutase mut or if there is a deficiency or a problem with processing vitamin b12 the cobalamin defects, cbl a,b, which is a cofactor of this enzyme. Urinary excretion of propionate metabolites fell significantly during the treatment in all subjects. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid. A wide range of genetic conditions was represented in the study population, such as metabolic disorders, proprionic acidemia, methylmalonic acidemia, arginosiccinic acidemia. The role of poor nutritional status and hyperhomocysteinemia in complicated pregnancy in syria pdf. Methylmalonic acid may be elevated due to inborn errors of metabolism.
Methylmalonic acidemia methelmalonic acideemeea is genetic disorder that affects how protein is broken down in the body. Up health system marquette laboratory methylmalonic acid. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental delay, excessive tiredness lethargy, an enlarged. Mouse model for methylmalonic acidemia, an inherited metabolic disorder methylmalonic acidemia mma is a metabolic disorder affecting 1 in 25,000 to 48,000 individuals globally. Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Clinical and genetic heterogeneity became evident very early when some patients responded to pharmacological doses of cobalamin vitamin b12 and others did not. Acidemia, methylmalonic nord national organization for. These inborn errors of amino acid metabolism have been studied extensively for decades. Methylmalonic acidemia an overview sciencedirect topics.
Methylmalonic acidemia article about methylmalonic. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. In folate deficiency, methylmalonic acid is normal. When the latter defect occurs in a proximal step that also impairs the. 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.
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