Propofol administration in patients with methylmalonic acidemia and. Methylmalonic acidemia is a disorder, passed down through families, in which the body cannot break down certain proteins and fats. They are caused by an enzymatic defect in the metabolism of four amino acids. Misidentification of propionic acid as ethylene glycol in a. Methylmalonic acidemia, methylmalonyl coenzyme a mutase, metabolic acidosis background methylmalonic acidemia mma is a metabolic disorder of organic acids in which methylmalonic acids accumulate due to inactivation of methylmalonyl coenzyme a mutase mcm. The pathophysiology likely reflects impaired energy metabolism in the mitochondria leading to neuronal toxicity in mma. This leads to a buildup of toxic substances and bouts of serious illness called decompensation events or metabolic crises. With each pregnancy, there is the same 25% chance of having a child with methylmalonic acidemia. Anaesthesia recommendations for patients suffering from. Methylmalonic acidemia is a disorder in which the body cannot break down certain proteins and fats. Perioperative care of children with inherited metabolic disorders grant stuart, frca. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia. Anesthetic management of a patient with methylmalonic. 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.
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. Pdf anaesthetic considerations for liver transplantation. Diag nosis of either condition usually depends on the identifica tion of metabolites by gas chromatography of body fluids, but by different methods. Promactin aa plus has a creamy, nonacid taste profile in an allnatural berry flavor. 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. This rare condition is associated with serious sequelae such as neurological manifestations andor even organ failure. Methylmalonic acidemia and intracellular cobalamin metabolism disorders represent a heterogeneous group of inborn errors of metabolism. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental delay, excessive tiredness.
Pdf anesthetic management of a patient with methylmalonic. Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. Methylmalonic acidemia mma describes a group of genetic, organic acid disorders in which the body is unable to breakdown certain proteins and fats. Methylmalonic acidemia adult metabolic diseases clinic. Oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma. This report describes an unusual case of a patient with mma. Methylmalonic acidemia is a form of ketotic hyperglycinemia.
Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. Perioperative care of children with inherited metabolic. 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, and cblx, or deficiency of the enzyme methylmalonylcoa epimerase. Anesthetic care of a child with propionic acidemia rafiq. Levocarnitine aids in the excretion of carnitine esters and repletes a relative deficiency. Patients are prescribed a protein restricted diet to prevent elevated levels methylmalonyl coa. 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 aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin cbl. Proposed guidelines for the diagnosis and management of. Methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. For more information on this disorder, choose ketotic hyperglycinemia as your search term in the rare disease database.
Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy. Anaesthesia recommendations for patients suffering from methylmalonic acidemia or aciduria disease name. Propionic acidemia is a very rare genetic form of ketotic hyperglycinemia. Most babies are diagnosed with the disease only after they get sick. Two types of mma that arenon responsive to vitamin b12 and caused by mutations in the mmacoa mutase mut gene are. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental. Jan 27, 2020 methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Because of secondary inhibition of propionylcoa carboxylase, propionic acid also accumulates, as do other organic acids. Methylmalonic acidemia genetics home reference nih. The patient presented today with methylmalonic acidemia provides us with an opportunity to discuss not only this condi. Methylmalonic acidemiamut information for health professionals.
Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. Preoperatively, there was no evidence of metabolic acidosis or electrolyte abnormalities. 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. Mma encompasses a heterogeneous group of disorders characterized by accumulation of. Promactin aa plus is a methionine, threonine, and valinefree, isoleucine low, nutritionally complete, readytodrink, amino acid based medical food for the dietary management of methylmalonic acidemia b12 nonresponsive or propionic acidemia. Department of health and human services recommends screening for this condition at birth because early detection and treatment has been shown to be beneficial. Methylmalonic acidemia diagnosis by laboratory methods.
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. The result is a buildup of a substance called methylmalonic acid in. Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy. Methylmalonic acidemia methelmalonic acideemeea is genetic disorder that affects how protein is broken down in the body. Clinical and genetic heterogeneity became evident very early when some patients responded to pharmacological doses of cobalamin vitamin b12 and others did not. Organic acids refer to the amino acids and certain oddchained fatty acids which are. May 19, 2015 methylmalonic acidemia and intracellular cobalamin metabolism disorders represent a heterogeneous group of inborn errors of metabolism. Methylmalonic coenzyme a mutase is a vitamin b 12dependent enzyme involved in the catabolism of leucine, isoleucine, and valine. These disorders are caused by mutations in the methylmalonylcoa mutase apoenzyme or by impaired synthesis of the enzymatic cofactor. Anesthesia for liver transplantation in a patient with. Hydroxycobalamin is used in b12 responsive variants. Pdf anaesthetic considerations for liver transplantation in.
The existing literature on the anesthetic management of mma and. Dec 26, 2018 methylmalonic acidemia is an inherited medical condition in which the body is unable to process certain proteins and fats causing a variety of complications. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism. Individuals with mma experience both acute and chronic neurological complications. Patients present either shortly after birth with acute deterioration. There is a 1 in 4, or 25% chance that two carriers of the gene will have a baby with methylmalonic acidemia. This app is designed to support families and children with mma on protein restricted diets. This case report provides information regarding propionic acidemia and its anesthetic management. Methylmalonic acidemia mma is a metabolic disorder of organic acids and is characterized by the accumulation of methylmalonic acids.
These complications which may be observed pretty soon after birth, may be mild to. The result is a build up of a substance called methylmalonic acid in the blood. Methylmalonic acidemia is listed as a rare disease by the office of rare diseases ord of the national institutes of health nih. Methylmalonic acidemia and intracellular cobalamin metabolism disorders. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening.
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 acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Methylmalonic acidemia nicklaus childrens hospital. It has been stated that propofol is contraindicated in this population. When patients with this disease present for surgery, their anesthetic must be tailored to meet their special needs. 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. Request pdf anesthesia for liver transplantation in a patient with methylmalonic acidemia liver transplantation is an accepted modality of treatment in some patients with inborn errors of. Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and lipids properly. Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy. Anesthetic management of a patient with methylmalonic acidemia. Methylmalonic acidemia mma is an organic acid disorder. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Mar 16, 2015 oberholzer et al and stokke et al reported the first patients with methylmalonic acidemia mma. Methylmalonic acidemia mma is a metabolic disorder of organic acids and is characterized by the accumulation of.
In mma, forced diuresis and alkalinisation of urine with sodium bicarbonate helps to eliminate methylmalonic acid due to its high renal clearance. This signs and symptoms information for acidemia, methylmalonic has been gathered from various sources, may not be fully accurate, and may not be the full list of acidemia, methylmalonic signs or acidemia, methylmalonic symptoms. Here are the ones the management for an acute decompensation in children and adults with methylmalonic acidemia due to a. Summary methymalonic acidemia mma is a hereditary metabolic. Methylmalonic acidemias are a subtype of organic acidemias that make the body unable to process certain proteins and fats properly. Methylmalonic aciduria due to methylmalonylcoa mutase. However, the anesthetic management of liver transplant for mma is not. Methylmalonic acidemia mma is a rare metabolic disorder that results as a consequence of the accumulation of toxic levels of methylmalonic acid. However, the anesthetic management of liver transplant for mma is not clear. These conditions, at one time designated as idiopathic acidosis of infancy, often result in lifethreatening acidbase disorders.
Methylmalonic acidemia is the biochemical hallmark of a group of autosomal recessive genetic metabolic disorders that prevent the body from converting lmethylmalonylcoa into succinylcoa. Methylmalonic acidemia is an inherited medical condition in which the body is unable to process certain proteins and fats causing a variety of complications. Implications propionic acidemia is a rare genetic disease associated with significant medical problems. Isolated methylmalonic aciduria is found in patients with mutations in the mut gene causing partial, mut, or complete, mut 0, enzyme deficiency. The management of methylmalonic aciduria includes a low protein diet avoiding an excess of isoleucine, methionine, threonine, valine, cholesterol, odd chain fatty acids, and an avoidance of long fasts. Methylmalonic acidemia with homocystinuria genetics home. Methylmalonic acidemia mma is a very rare genetic disease of metabolism that progressively leads to neurological and renal sequelae. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Fuchshuber a, mucha b, baumgartner er, vollmer m, hildebrandt f 2000 mut0 methylmalonic acidemia. The efficacy of liver transplantation for mma was recently reported. 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 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.
Anaesthesia should not be undertaken lightly and the risks of anaesthesia must be carefully considered and explained to the parents and the child if appropriate along with the benefits of the scheduled procedure. Metabolic phenotype of methylmalonic acidemia in mice and. Nemch methylmalonic acidemia is one of the inborn errors capable of producing severe ketoacidosis. Anaesthetic considerations for liver transplantation in propionic acidemia article pdf available in indian journal of anaesthesia 601. Most patients will require diagnostic andor therapeutic procedures frequently requiring sedation or anesthetic management due to neurological and neurocognitive impairments.
Methymalonic acidemia mma is a hereditary metabolic disorder characterized by a defect of the methylmalonyl. About 1 in 20 000 babies are born with methylmalonic acidemia each year in canada. Methylmalonic acidemia is an inherited illness in which the body doesnt metabolize protein correctly. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid due to deficiency of methylmalonylcoa. Signs and symptoms of this condition usually appear in early infancy and include vomiting, dehydration, hypotonia, lethargy, and failure to thrive.
It consists of a group of biochemically and ge netically distinct disorders that produces a block in the con version of methylmalonyicoa to succinyicoa, with conse. Propofol administration in patients with methylmalonic. The patient was a 19yearold female diagnosed with severe mma at 3 days of age, who was scheduled for renal replacement therapy. Doctors dont usually test newborns for methylmalonic acidemia, but because it may cause the. Isolated methylmalonic acidemia mma refers to a group of inborn errors of organic acid metabolism caused by impaired conversion of methylmalonylcoa to succinylcoa. Methelmalonic acidureea is genetic disorder that affects how protein is broken down in the body. Anaesthetic considerations in a patient with methylmalonyl. Acidemia, methylmalonic nord national organization for. Combined liverkidney transplant for the management of. The pathophysiology likely reflects impaired energy metabolism in the mitochondria leading to neuronal toxicity in. Anaesthesia for liver transplantation in a patient with methylmalonic acidemia. Methylmalonic aciduria, mma, isolated methylmalonic acidemia methylmalonic acidemia mma is a group of rare approx.
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 the branchedchain amino acids include isoleucine, leucine and valine. 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. Furthermore, signs and symptoms of acidemia, methylmalonic may vary on an individual basis for each patient. Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy lethargy. These complications which may be observed pretty soon after birth, may be mild to even potentially life threatening. Methylmalonic acidemia mma is a genetic disorder caused by a deficiency in the methylmalonylcoa mutase mcm enzyme. Methylmalonic acidemia what is methylmalonic acidemia. Isolated methylmalonic acidemiaaciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. 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 and propionic acidemia mmapa are inborn errors of. Table considerations and management of general anesthesia. Understanding methylmalonic acidemia what is methylmalonic acidemia. The result is a buildup of a substance called methylmalonic acid in the blood.
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