Methylmalonic acidemia diagnosis by laboratory methods ncbi. These inborn errors of amino acid metabolism have been studied extensively for decades. In 14 patients with methylmalonic acidemia we studied the correlations between clinical severity considered in terms of survival and number of acute episodes, daily. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental delay, excessive tiredness lethargy, an enlarged.
The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening. In folate deficiency, methylmalonic acid is normal. Diet calculations are demonstrated at the end of the presentation. The result is a build up of a substance called methylmalonic acid in the blood. Methylmalonic acidemia definition of methylmalonic. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats.
Methylmalonic acidemia with homocystinuria genetics home. Isolated methylmalonic acidemia aciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. Use is restricted in the same manner as that defined in the mksap 16 digital license agreement. Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant. Doctors dont usually test newborns for methylmalonic acidemia, but because it may cause the. High blood and urine levels of methylmalonic acid and propionic acid. Methylmalonic acidemia kansas department of health. Causes of and diagnostic approach to methylmalonic acidurias core.
Current role of liver transplantation for methylmalonic acidemia. Methylmalonic acid mma is a substance produced in very small amounts and is necessary for human metabolism and energy production. Clinical and genetic heterogeneity became evident very early when some patients responded to pharmacological doses of cobalamin vitamin b12 and others did not. Jun 05, 2018 the methylmalonic acid test is a simple blood test. Oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma. Methylmalonic acidemia is a disorder, passed down through families, in which the body cannot break down certain proteins and fats. There is a 1 in 4, or 25% chance that two carriers of the gene will have a baby with methylmalonic acidemia. Methylmalonic acid levels in nonelderly adult chronic ppi. Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria cblc. A megamitochondrial disorder affecting the kidney article pdf available in pediatric nephrology 2911 may 2014 with 240 reads how we measure reads.
Methylmalonic acid is detectable in the urine by a relatively simple chemical test or by paper chromatography with staining by 0dianisidine fast blue b. Sakamoto r, nakamura k, kido j, matsumoto s, mitsubuchi h, inomata y, endo f. This leads to a buildup of toxic substances and bouts of serious illness called decompensation events or metabolic crises. Click on the image or right click to open the source website in a. The role of poor nutritional status and hyperhomocysteinemia in complicated pregnancy in syria pdf.
Methylmalonic acidemia methelmalonic acideemeea is genetic disorder that affects how protein is broken down in the body. Methylmalonic acidemias can usually be diagnosed before birth prenatally by measuring the concentration of methylmalonic acid in amniotic fluid or activity of the deficient enzyme in fluid or tissue samples obtained from the fetus or uterus during pregnancy amniocentesis or chorionic villus sampling cvs. 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. Study findings can immediately be applied to human patients with the disease. Urinary methylmalonic acid levels determined vitamin b.
Patients present either shortly after birth with acute deterioration. Mitochondrial dysfunction in mut methylmalonic acidemia article pdf available in the faseb journal 234. Elevated hormone flags liver problems in mice with methylmalonic acidemia. Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. Methylmalonic acidemia mma is usually caused by a deficiency of the enzyme methylmalonylcoa mutase mcm, a defect in the transport or synthesis of its. In some families, there may be only one child with. With each pregnancy, there is the same 25% chance of having a child with methylmalonic acidemia. Methylmalonic and propionic acidemia mmapa are autosomal recessive disorders of propionate catabolism caused by defects in the enzymes methylmalonylcoa mutase mut or propionylcoa carboxylase pcc characterized by accumulation of metabolites of branchedchain amino acid catabolism such as 3hydroxypropionic acid, methylcitric acid andor methylmalonic acid in plasma, urine and other. Bruce barshop and his clinical staff in the division of metabolic genetics at the university of california san diego school of medicine, a deficiency in the bodys metabolism of methylmalonic acid, a type of amino acid, causes methylmalonic acidemia.
Methylmalonic acidemia genetics home reference nih. An elevated serum methylmalonic acid level is more sensitive and specific for diagnosing cobalamin vitamin b 12 deficiency than a low serum vitamin b 12 level this content is excerpted from mksap 16 with permission from the american college of physicians acp. The patient, 6 years old at the time of the report, was born at. The methylmalonic acid test is a simple blood test.
Methylmalonic aciduria, mma, isolated methylmalonic acidemia methylmalonic acidemia mma is a group of rare approx. High levels of methylmalonic acid may indicate a vitamin b12 deficiency. Methylmalonic acidemias can usually be diagnosed before birth prenatally by measuring the concentration of methylmalonic acid in amniotic fluid or activity of the deficient enzyme in fluid or tissue samples obtained from the fetus or uterus during pregnancy amniocentesis or. Methylmalonic acidemia mma is a genetic disorder caused by a deficiency in the methylmalonylcoa mutase mcm enzyme. Jan 27, 2020 methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Optic neuropathy in methylmalonic acidemia and propionic.
Newborn screening for methylmalonic aciduria by tandem. In adults, moderately time elevated values are indicative of cobalamin deficiency. Methylmalonic acidemia mut information for health professionals. Diagnosing vitamin b12 deficiency with methylmalonic acid. Methylmalonic acidemia adult metabolic diseases clinic. Optic neuropathy on has been increasingly recognised in both conditions, mostly through isolated case reports or small cases series.
Thediagnosis of methylmalonic acidemia is often suspected on clinical grounds, and it is readily confirmed by laboratory studies. 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. Monitoring of vitamin b12 nutritional status in the united states by using plasma methylmalonic acid and serum vitamin b12. The patient, 6 years old at the time of the report, was born at 34 weeks gestation to nonconsanguineous parents. Analysis of urine methylmalonic acid, plasma homocystine, and growth of two unrelated patients with cobalamin c disease who were initially receiving cyanocobalamin and were subsequently switched to hydroxocobalamin. Patients present either shortly after birth with acute. Urinary methylmalonic acid levels were within the normal range for all study participants. Methylmalonic acid mma in plasma or serum is widely used for assessment of vitamin b12 status. Methylmalonic acidemia nicklaus childrens hospital.
Pdf methylmalonic acidemia with emergency hypertension. Methylmalonic acidemias are a subtype of organic acidemias that make the body unable to process certain proteins and fats properly. 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 propionic acidemia are two organic acidemias. These images are a random sampling from a bing search on the term methylmalonic acidemia. Two types of mma that arenon responsive to vitamin b12 and caused by mutations in the mmacoa mutase mut gene are.
Methylmalonic aciduria mma comprises a heterogeneous group of disorders, which are characterized by accumulation of methylmalonate in the body due to deficiency of methylmalonyl coenzyme a mutase mcm, ec 5. In one step of metabolism, vitamin b12 promotes the conversion of methylmalonyl coa a form of mma to succinyl coenzyme a. Patients are prescribed a protein restricted diet to prevent elevated levels methylmalonyl coa. Background methylmalonic acidemia mma and propionic acidemia pa are rare hereditary disorders of protein metabolism, manifesting early in life with ketoacidosis and encephalopathy and often resulting in chronic complications. A symptomfree period is typical in methylmalonic acidemia with homocystinuria, since for clinical symptoms to appear, protein intake is required, with the.
Fran tena 9 diciembre, 2018 9 diciembre, 2018 general 0. Gas chromatography confirms the identity of the mma. Methylmalonic acidemia is a disorder in which the body cannot break down certain proteins and fats. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental. Here are the ones the management for an acute decompensation in children and adults with methylmalonic acidemia due to a. These autosomal recessive disorders result from deficient activity of methylmalonyl. Most babies are diagnosed with the disease only after they get sick. Kasahara m1, horikawa r, tagawa m, uemoto s, yokoyama s, shibata y, kawano t, kuroda t, honna t, tanaka k, saeki m. The result is a buildup of a substance called methylmalonic acid in the blood. Pdf mitochondrial dysfunction in mut methylmalonic acidemia. About 1 in 20 000 babies are born with methylmalonic acidemia each year in canada.
Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid due to deficiency of methylmalonylcoa. Methylmalonic and propionic aciduria pa are the most frequent forms of branched. Biochemical and clinical response to hydroxocobalamin. At the center for rare disease therapy, every child diagnosed with a rare disease receives an individualized treatment plan and familycentered care. Methylmalonic acidemia what is methylmalonic acidemia. Started in 1995, this collection now contains 6769 interlinked topic pages divided into a tree of 31 specialty books and 732 chapters. Diet, nutritional status, and age should be considered in the evaluation of serum mma level. Plasma amino acids usually show severe hyperglycinemia 6001,200 mm in patients beyond the neonatal period.
Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Methylmalonic acidemia mma is an organic acid disorder. Doctors give unbiased, helpful information on indications, contraindications, benefits, and complications. Current role of liver transplantation for methylmalonic. Vitamin b12unresponsive methylmalonic acidemia is an inborn error of vitamin b12 cobalamin. 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. Isolated methylmalonic acidemiaaciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. Pdf proposed guidelines for the diagnosis and management. 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 is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. Proposed guidelines for the diagnosis and management of. Methylmalonic acidemia diagnosis by laboratory methods. Through clinical and scientific study, researchers have been able to elucidate the biochemistry and cell biology that underlies these two diseases.
Download fulltext pdf download fulltext pdf methylmalonic acidemia with emergency hypertension article pdf available in nefrologia. Liquid chromatographytandem mass spectrometry stable isotope dilution analysis lc. The range of methylmalonic acid in plasma or serum from healthy adults is 0. To compare the therapeutic effectiveness of hydroxocobalamin and cyanocobalamin in patients with combined methylmalonic acidemia and homocystinuria. Bailey rl, carmel r, green r, pfeiffer cm, cogswell me, osterloh jd et al. Genetics of methylmalonic acidemia clinical presentation.
Methylmalonic acid may be elevated due to inborn errors of metabolism. Methylmalonic acidemia an overview sciencedirect topics. All structured data from the file and property namespaces is available under the creative commons cc0 license. Methylmalonic aciduria, mma, isolated methylmalonic acidemia. 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. Enzyme assay in wbc ppa, dna testing 2 genes for ppa, gene panel for mma. Nov 11, 2014 at the center for rare disease therapy, every child diagnosed with a rare disease receives an individualized treatment plan and familycentered care. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated. Learn more about b12 and the symptoms of vitamin b12 deficiency here. Methylmalonic acid is used to detect vitamin b12 deficiency. Mary sowa, ms, rd dietitian, metabolic clinic, choc childrens the course on propionic and methylmalonic acidemia includes information on diseasespecific biochemistry, nutrition management and monitoring. Mar 16, 2015 oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma.
Acidemia, methylmalonic nord national organization for. Prevalence of 148,000161,000 has been reported for methylmalonic aciduria of all causes in. 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. If a metabolic crisis is not treated, a child with mma can develop. Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy lethargy. This page was last edited on september 2009, at 05. There was no significant difference in urinary methylmalonic acid levels between the proton pump users mdn1.
This app is designed to support families and children with mma on protein restricted diets. Files are available under licenses specified on their description page. When the latter defect occurs in a proximal step that also impairs the. Acidemia metilmalonica con homocistinuria soy muy valiente. 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. 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. They are caused by an enzymatic defect in the metabolism of four.
Methylmalonic acid and homocysteine as indicators of. Vitamin b12 unresponsive methylmalonic acidemia orphanet. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by. Mmaa is involved in the synthesis of adenosylcobalamin adocbl, a coenzyme for methylmalonylcoa mutase mut. Methylmalonic acidemiamut information for health professionals. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria.
1090 11 392 263 68 1604 1299 1348 1510 295 1602 433 26 868 1588 597 1351 451 230 1157 953 1524 388 1599 37 1305 1303 1100 1337 537 318 1005 742 673 672