C3 may also be elevated in cases of multiple carboxylase deficiency mcd. To describe the clinical and biochemical features and longterm outcome of a cohort of eight patients with methylmalonic acidemia and homocystinuria cblc. Successful perioperative management of livingdonor liver. Early liver transplantation for neonatalonset methylmalonic. Methylmalonic acidemia definition of methylmalonic. Implications for the management of patients with propionic acidemia and methylmalonic. Methylmalonic acidemia mma is an organic acid disorder. The goal of this activity is to provide clinicians with the knowledge to suspect an organic acidemia as the cause of a patients acute illness.
Background patients with propionic acidemia usually present in the neonatal period with lifethreatening ketoacidosis, often complicated by hyperammonemia. This test is useful for the diagnosis of patients who are suspected to. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for methylmalonic acidemia. Evaluating individuals with signs and symptoms associated with a variety of causes of. Methylmalonic acidemia genetic and rare diseases information.
In 14 patients with methylmalonic acidemia we studied the correlations between clinical severity considered in terms of survival and number of acute episodes, daily. This leads to a buildup of toxic substances and bouts of serious illness called decompensation events or metabolic crises. Isolated mma is primarily caused by the deficiency of methylmalonylcoa mutase mma mut. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia.
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. Longterm outcome in treated combined methylmalonic. Methylmalonic acidemia mma is a rare genetic metabolic disease, and most of its cases are autosomal recessive. 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. Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy lethargy. Fran tena 9 diciembre, 2018 9 diciembre, 2018 general 0.
Nemch methylmalonic acidemia is one of the inborn errors capable of producing severe ketoacidosis. Background methylmalonic acidemia mma and propionic acidemia pa are rare hereditary disorders of protein metabolism, manifesting early in life with ketoacidosis and. Methylmalonic acidemia genetics home reference nih. With each pregnancy, there is the same 25% chance of having a child with methylmalonic acidemia. 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 cbl a,b information for health professionals. Elevated hormone flags liver problems in mice with methylmalonic acidemia. Methylmalonic acidemiaaciduria mma is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid. Acidemia metilmalonica con homocistinuria soy muy valiente. 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. Patients present either shortly after birth with acute deterioration. Methylmalonic acidemia, methylmalonic aciduria, propionic. 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.
It is estimated that the incidence of mma in western populations ranges from 1. 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. Glutaricaciduria ii glutaric acidemia ii occurs in two forms during two different stages of life. Neurologic nonmetabolic presentation of propionic acidemia. Methylmalonic and propionic acidemia mmapa are autosomal recessive disorders of propionate catabolism caused by defects in the enzymes methylmalonylcoa mutase mut or propionylcoa. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism. 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 affects boys and girls equally. For more information on this disorder, choose ketotic hyperglycinemia as your search term in the rare disease database. It shares some clinical and biochemical features with propionic acidemia because methylmalonyl. Methylmalonic acidemia aciduria mma is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid.
Two types of mma that arenon responsive to vitamin b12 and caused by mutations in the mmacoa mutase mut gene are. 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. 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. This rare condition is associated with serious sequelae such as neurological manifestations andor even organ failure. Elevated hormone flags liver problems in mice with methylmalonic. Symptoms babies may appear normal at birth, but develop symptoms once they start eating more protein, which can cause the condition to get worse. 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. Methylmalonic acidemia mma is a metabolic disorder of organic acids and is characterized by the accumulation of methylmalonic acids. Sep 02, 2014 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. Recognition and treatment of organic acidemias cmece. Propionic acidemia is a very rare genetic form of ketotic hyperglycinemia. It is estimated that the incidence of mma in western.
This leads to a buildup of toxic substances and bouts of. Acidemia, methylmalonic nord national organization for. This test is useful for the diagnosis of patients who are suspected to have methylmalonic acidemia according to clinical symptoms, biochemical findings, or abnormal newbornscreening results. 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. Methylmalonic acidemia is a 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. Department of medicine, university of toronto, toronto. Methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Methylmalonic acidemia information mount sinai new york. In some families, there may be only one child with. Learning objectives upon completion of this activity, participants will be able to. Other biochemical abnormalities were hyperglycinemia, hyperglycinuria, and hyperlactatemia. Methylmalonic acidemia with homocystinuria genetics home. The invitae methylmalonic acidemia panel analyzes up to 18 genes that are associated with methylmalonic acidemia. Vitamin b12 responsive forms include cobalamin a cbla and cobalamin b cblb deficiencies. A typical episode is ushered in with ketonuria and vomiting, followed by acidosis, dehydration, and lethargy, leading, in the absence of aggressive treatment, to coma and death. Methylmalonic acidemia mimicking diabetic ketoacidosis in.
Methylmalonic acidemiapropionic acidemia orphanet journal of. Methylmalonic acidemia mmaemia is a rare hereditary disease caused by the accumulation of methylmalonic acid mma due to metabolic disorders related to methylmalonylcoa. Proposed guidelines for the diagnosis and management of. Methylmalonic acidemia mut information for health professionals. Methylmalonic acidemia mma is an inherited organic acidemia usually present with recurrent episodes of acute illness. Isolated methylmalonic acidemia aciduria mma is a devastating metabolic disorder with poor outcomes despite current medical treatments. 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 mma is a rare metabolic disorder that results as a consequence of the accumulation of toxic levels of methylmalonic acid. Isolated methylmalonic acidemiaaciduria mma is a devastating metabolic disorder with poor outcomes despite current medical treatments. Excretion of methylmalonate a product of amino acid metabolism in the urine is abnormally high. Read more about symptoms, diagnosis, treatment, complications, causes and. A wide range of genetic conditions was represented in the study population, such as metabolic disorders, proprionic acidemia, methylmalonic acidemia, arginosiccinic acidemia.
Preoperatively, there was no evidence of metabolic acidosis or electrolyte abnormalities. 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 kansas department of health. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the. The effects of methylmalonic acidemia, which usually.
The value of liver transplantation for methylmalonic acidemia. With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalaminunresponsive methylmalonylcoa mutase mcm deficiency is characterized by the. Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. Optic neuropathy in methylmalonic acidemia and propionic acidemia. When the latter defect occurs in a proximal step that also impairs the. 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 fat.
Methylmalonic acidemia mimicking diabetic ketoacidosis in an. The patient excreted large amounts of methylmalonic acid in the urine and the blood level was elevated. Jan 27, 2020 methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Pa and severe cases of mut may be lifethreatening in the first few days of life. 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. Most patients with isolated methylmalonic acidemia mma propionic acidemia pa presenting during the. Mitochondrial dysfunction in mut methylmalonic acidemia article pdf available in the faseb journal 234. A typical episode is ushered in with ketonuria and vomiting, followed by acidosis. Methylmalonic acidemia diagnosis by laboratory methods. Recognize clinical presentations of organic acidemias, including methylmalonic acidemia mma and propionic. Methylmalonic acidemia synonyms, methylmalonic acidemia pronunciation, methylmalonic acidemia translation, english dictionary definition of methylmalonic acidemia. Methylmalonic acidemia is a disorder in which the body cannot break down certain proteins and fats. Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Optic neuropathy in methylmalonic acidemia and propionic.
Implications for the management of patients with propionic acidemia and. 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. Like other mitochondrial enzymopathies, enzyme replacement therapy ert is not available, and although promising, aav gene therapy can be limited by preexisting immunity and has been associated with genotoxicity in mice. Methylmalonic acidemia is a rare autosomal recessive inborn error of metabolism that typically manifests in infancy with. Pdf proposed guidelines for the diagnosis and management.
Methylmalonic acidemiamut information for health professionals. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid due to deficiency of. Methylmalonic acidemia an overview sciencedirect topics. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental. Anesthetic management of a patient with methylmalonic. Methylmalonic acidemia article about methylmalonic. Methylmalonic acidemia mma and propionic acidemia pa are two of the most common organic acidemias oa. Learning objectives upon completion of this activity, participants will. Mouse model for methylmalonic acidemia, an inherited. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental delay, excessive tiredness lethargy, an enlarged.
The united states department of health and human services recommends screening for this condition at birth. Methylmalonic acidemia is an autosomal recessive disorder of amino acid metabolism, involving a defect in the conversion of methylmalonylcoenzyme a coa to succinylcoa. Here are the ones the management for an acute decompensation in children and adults with methylmalonic acidemia due to a. Acidemia isovaleric nord national organization for rare. 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. For more information, choose methylmalonic acidemia as your search term in the rare disease database. Isolated methylmalonic acidemiaaciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. Download fulltext pdf download fulltext pdf methylmalonic acidemia with emergency hypertension article pdf available in nefrologia.
Methylmalonic acidemia can be caused by an inherited deficiency of methylmalonylcoa mutase, an adenosylcobalaminrequiring enzyme that converts lmethylmalonylcoa to succinylcoa figure 975. The result is a buildup of a substance called methylmalonic acid in the blood. Mary sowa, ms, rd dietitian, metabolic clinic, choc childrens the course on propionic and methylmalonic acidemia includes information on disease. Pdf mitochondrial dysfunction in mut methylmalonic acidemia. Testing for methylmalonic acidemia is often done as part of a newborn screening exam. Evaluating children with signs and symptoms of methylmalonic acidemia. Pdf methylmalonic acidemia with emergency hypertension. There is a 1 in 4, or 25% chance that two carriers of the gene will have a baby with methylmalonic acidemia. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening. Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. Longterm outcome in treated combined methylmalonic acidemia. Isolated methylmalonic acidemia aciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase mut 0 enzymatic subtype or mut. Glutaricaciduria ii glutaric acidemia ii occurs in two forms during two different stages of.