Methylmalonic acidemia, an autosomal recessive disorder, is caused by a deficiency of a specific enzyme on the catabolic pathway of certain amino acids isoleucine, valine, threonine and methionine. Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin cbl. Propionic acidemia has been reported in 2 families of amish ancestry in a single large mennonite amish kindred. Because iems can present acutely with lifethreatening crises that require specific interventions, it is critical for the emergency medicine physicians, pediatricians, internists, and critical care physicians as well as biochemical geneticists to be familiar with the initial assessment and management of patients with these disorders. Variable dietary management of methylmalonic acidemia. Vitamin b12 responsive forms include cobalamin a cbla and cobalamin b cblb deficiencies. Acidemia, methylmalonic nord national organization for. A wide range of genetic conditions was represented in the study population, such as metabolic disorders, proprionic acidemia, methylmalonic acidemia, arginosiccinic acidemia. Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy lethargy. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental delay, excessive tiredness lethargy, an enlarged. Methylmalonic acidemia mma and propionic acidemia pa are two of the most common organic acidemias oa. This may occur alone or in combination with other biochemical abnormalities such as elevation of homocysteine and low methionine.
Methylmalonic acidemia an overview sciencedirect topics. 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 is an autosomal recessive disorder of amino acid metabolism, involving a defect in the conversion of methylmalonylcoenzyme a coa to succinylcoa. Doctors dont usually test newborns for methylmalonic acidemia, but because it may cause the unexplained deaths and serious illnesses of some babies, many states are now thinking of including it among the many diseases for which doctors and midwives screen infants immediately after birth. Methylmalonic acidemia mma is an autosomal recessively inherited organic acid disorder due to deficient activity of mitochondrial. Pa and severe cases of mut may be lifethreatening in the first few days of life. Noninvasive prenatal test of methylmalonic academia cblc type. In some families, there may be only one child with. Methylmalonic acidemia nicklaus childrens hospital. Patients are prescribed a protein restricted diet to prevent elevated levels methylmalonyl coa. An inborn error of metabolism leading to chronic metabolic acidosis. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the. 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 mma is an organic acid disorder.
Fran tena 9 diciembre, 2018 9 diciembre, 2018 general 0. Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. Mobilization of free fatty acids from stores to the liver produces a fatty liver. Review open access proposed guidelines for the diagnosis. Methylmalonic acidemia mma is a rare genetic metabolic disease, and most of its cases are autosomal recessive. For more information on this disorder, choose ketotic hyperglycinemia as your search term in the rare disease database. Methylmalonic acidemia is listed as a rare disease by the office of rare diseases ord of the national institutes of health nih. Methylmalonic acidemia diagnosis by laboratory methods. Acidemia metilmalonica con homocistinuria soy muy valiente. Novel insights into the pathophysiology of kidney disease in. Treatment includes aggressive management of decompensation events, a lowprotein diet, certain medications, antibiotics and, in some cases, liver and kidney transplantation. Twenty patients 10 males and 10 females with methylmalonic acidemia were included in this study. Methylmalonic acidemia is a disorder, passed down through families, in which the body cannot break down certain proteins and fats. Methylmalonic acidemia mma is a lethal, severe heterogeneous disorder of.
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. Methylmalonic acidemia adult metabolic diseases clinic. Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Different forms of isolated methylmalonic aciduria have been classified according to complementation groups of cells in vitro. The branchedchain amino acids include isoleucine, leucine and valine. Methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Selective necrosis of the globus pallidus is an important mri finding in mma. Methylmalonic acidemia is a form of ketotic hyperglycinemia.
All patients had dramatic reduction of plasma free homocystine and urine. About 1 in 20 000 babies are born with methylmalonic acidemia each year in canada. Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. Methylmalonic aciduria due to methylmalonylcoa mutase deficiency. Oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma. This means that methylmalonic acidemia, or a subtype of methylmalonic acidemia, affects less than 200,000 people in the us population. 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. Methylmalonic acidemia synonyms, methylmalonic acidemia pronunciation, methylmalonic acidemia translation, english dictionary definition of methylmalonic acidemia. Proposed guidelines for the diagnosis and management of.
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. C3 may also be elevated in cases of multiple carboxylase deficiency mcd. With each pregnancy, there is the same 25% chance of having a child with methylmalonic acidemia. The product provides all other essential amino acids as well as nonessential amino acids, carbohydrate, fat, essential fatty acids, vitamins and minerals.
Elevated hormone flags liver problems in mice with methylmalonic acidemia. Early liver transplantation for neonatalonset methylmalonic. Sep 24, 2018 noninvasive prenatal test of methylmalonic academia cblc type through targeted sequencing of cell free dna in maternal plasma lianshu han, chao chen, fengyu guo, jun ye, zhiyu peng, wenjuan qiu, yaoshen wang, wei li, huiwen zhang, lili liang, yu wang, huanhuan wang, xing ji, jun sun, xuefan gu. Clinical presentations, diagnosis and management nuria carrillocarrasco, randy j. Clinical and genetic heterogeneity became evident very early when some patients responded to pharmacological doses of cobalamin vitamin b12 and others did not. 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.
They are inherited defects of the catabolism of propionate, a common intermediate product of the catabolism of branchedchain amino acids and odd chain fatty acids, caused by variable deficient activity of two mitochondrialocated enzymes. Methylmalonic acidemia cbl a,b information for health professionals. There is a 1 in 4, or 25% chance that two carriers of the gene will have a baby with methylmalonic acidemia. In methylmalonic acidemia and propionic acidemia patients, the proportion of propionate generated from each source is somewhere around 50% from amino acids, and either 20%30% bacteriafatty acids 11. Oa 1 is a medical food powder that is free of the essential amino acids isoleucine, methionine, threonine, and valine for children with propionic or methylmalonic acidemia organic acidemia. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic 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. This leads to a buildup of toxic substances and bouts of serious illness called decompensation events or metabolic crises. Methylmalonic acidemia methelmalonic acideemeea is genetic disorder that affects how protein is broken down in the body. With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalaminunresponsive methylmalonylcoa mutase mcm deficiency is characterized by the persistent risk of recurrent lifethreatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma. Methylmalonic acidemia genetics home reference nih. Noninvasive prenatal test of methylmalonic academia cblc type through targeted sequencing of cell free dna in maternal plasma lianshu han, chao chen, fengyu guo, jun ye, zhiyu peng, wenjuan qiu, yaoshen wang, wei li, huiwen zhang, lili liang, yu wang, huanhuan wang, xing ji, jun sun, xuefan gu. Methylmalonic acidemia mma is a group of disorders characterized by the accumulation of methylmalonic acid in the fluids of the affected individual. Propionic acidemia is a very rare genetic form of ketotic hyperglycinemia.
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. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by. Liver transplant has been proposed as an alternative treatment and anecdotally attempted. May 28, 2016 patients and their families work with nih researchers to advance research on methylmalonic acidemia duration. This app is designed to support families and children with mma on protein restricted diets. Review open access proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia matthias r baumgartner1, friederike horster2, carlo dionisivici7, goknur haliloglu10, daniela karall, kimberly a chapman6, martina huemer1, michel hochuli11, murielle assoun3, diana ballhausen4, alberto burlina5, brian fowler1, sarah c grunert8, stephanie grunewald9. Isolated methylmalonic acidemias mmas are a group of autosomal recessive inborn errors of metabolism representative of metabolic disorders that feature a block near the terminal oxidation step of substrates feeding into the propionate pathway, primarily the branched chain amino acids, isoleucine and valine, but also threonine, methionine, odd chain fatty acids, and cholesterol. Mobilized free fatty acids from body fat enter the liver resulting in a fatty liver. The first recognized cases of these disorders were described in 1967. Venditti nuria carrillocarrasco, organic acid research section, genetics and molecular biology branch, national human genome research institute, national institutes of. Methylmalonic acidemia diagnosis by laboratory methods ncbi. Nutrition support of infants and toddlers with propionic or methylmalonic acidemia. Methylmalonic acidemia, cobalamin c type, presenting with.
Methylmalonic acidemia mma is usually caused by a deficiency of the enzyme methylmalonylcoa mutase mcm, a defect in the transport or synthesis of its. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental. Methylmalonic aciduria, mma, isolated methylmalonic acidemia. Mar 16, 2015 oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma. Methylmalonic acidemia definition of methylmalonic acidemia. Isolated methylmalonic aciduria is found in patients with mutations in the mut gene causing partial, mut, or complete, mut 0, enzyme deficiency. Longterm outcome in treated combined methylmalonic acidemia. National human genome research institute 2,887 views.
Combined methylmalonic acidemia and homocystinuria, cblc type. After a symptomfree period there is a rapid decline of well. Methylmalonic acidemia new england consortium of metabolic. Twentyfive percent of patients had a history of hospitalization because of icter or prematurity. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening. Optic neuropathy in methylmalonic acidemia and propionic acidemia. Methylmalonic acidemia, cobalamin c type, was subsequently diagnosed in both cases. Methylmalonic aciduria mma is a rare inborn error of metabolism due to the mutation of the.
Organic acidemia, is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branchedchain amino acids, causing a buildup of acids which are usually not present. Neurologic nonmetabolic presentation of propionic acidemia. The increased organic acids may also be toxic to hepatocytes. Isolated methylmalonic acidemiaaciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. Nemch methylmalonic acidemia is one of the inborn errors capable of producing severe ketoacidosis. Treatment includes aggressive management of decompensation events, a lowprotein diet, certain medications, antibiotics and.
The value of liver transplantation for methylmalonic acidemia. It is estimated that the incidence of mma in western populations ranges from 1. Methylmalonic acidemia is a disorder in which the body cannot break down certain proteins and fats. Here are the ones the management for an acute decompensation in children and adults with methylmalonic acidemia due to a. Patients and their families work with nih researchers to advance research on methylmalonic acidemia duration. All known genetic forms of mma are nonsex linked autosomal and recessive. The result is a buildup of a substance called methylmalonic acid in the blood. Propimex 1 amino acidmodified infant formula with iron. Understanding acute metabolic decompensation in propionic and. 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. An erosive, desquamating dermatitis with histopathologic characteristics resembling acrodermatitis enteropathica may be a presenting sign in cobalamin c methylmalonic acidemia, even in the absence of longstanding nutritional restrictions or deficiency. Pdf isolated methylmalonic acidemiaaciduria is caused by complete or. Methylmalonic acidemia mma is a genetic disorder caused by a deficiency in the methylmalonylcoa mutase mcm enzyme. Methylmalonic acidemia is caused by changes in several different genes and is inherited in an autosomal recessive fashion.
Isolated methylmalonic acidemia aciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. Jan 27, 2020 methylmalonic acidemia is caused by changes in several different genes and is inherited in an autosomal recessive fashion. Methylmalonic acidemia mma is an autosomal recessive disorder treated with precursorfree medical food while. Propionylcarnitine c3 is an important biomarker for the detection of propionic acidemia pa, methylmalonic acidemia mut, and the cobalamin disorders cbl a,b, and cbl c,d. Methylmalonic acidemia with homocystinuria genetics home.
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