Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats lipids properly. Methylmalonic acidemia an overview sciencedirect topics. He was treated with vit b12 and carnitine supplements and has been on followup for the last 3 years. Methylmalonic acid an overview sciencedirect topics. Vitamin b12 responsive forms include cobalamin a cbla and cobalamin b cblb deficiencies. Methylmalonic acidemia refers to a group of inherited conditions in which the body cant breakdown certain parts of proteins and fats. Clinical presentation, molecular analysis and followup of patients. Mma levels in urine range from 1020 mmolmol creatinine in mild disturbances of mma metabolism to.
Methylmalonic acidemia can be caused by mutations or mistakes in several genes. The disease has a poor outcome marked by early mortality preceded by a coma. Mma is also a specific diagnostic marker for the group of disorders collectively called methylmalonic acidemia, which include at least 7 different complementation groups. Erosive dermatitis resembling the skin lesions of acrodermatitis enteropathica has been described in a number of aminoacidopathies and organic acidemias. Methylmalonic acidemia homocystinuria is caused by anomalies in the synthesis of both adenosylcobalamin adocbl and of methylcobalamin mecbl resulting from genetic defects in the cbl complementation classes c, d, f and j. This leads to a buildup of toxic substances and bouts of serious illness called decompensation events or metabolic crises. Methylmalonic aciduria was treated according to standard therapies low protein diet, lcarnitine, and. Methylmalonic acid mma is a metabolic intermediate in the biosynthesis of succinic acid from propionic acid, a step that involves the enzyme methylmalonyl coenzyme a mutase and a vitamin b12derived cofactor. Pdf isolated methylmalonic acidemia aciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase. Diagnostic dilemma of patients with methylmalonic aciduria. Treatment of methylmalonic acidemia by liver or combined liverkidney transplantation. Dysfunction of mut leads to an accumulation of methylmalonic acid mma. The nationwide newborn screening for mma pa has been in place in taiwan from january, 2000 and. Cblc is caused by mutations in the mmachc gene 1p36.
Two types of mma that arenon responsive to vitamin b12 and caused by mutations in the mmacoa mutase mut gene are. Methylmalonic and propionic aciduria pa are the most frequent forms of branched. Association of methylmalonic acidemia and erythema nodosum dear editor, methylmalonic acidemia, one of the organic acidemias, is associated with a variety of clinical presentations ranging from very sick newborn infants to asymptomatic adults, regardless of the nature of the enzymatic defect or the biochemical abnormalities. Methylmalonic aciduria was treated according to standard therapies low protein diet, lcarnitine, and hydroxycobalamin. Methylmalonic acidemia mma is a condition with many different forms, all of which have different causes and treatments. If the body is missing an enzyme needed to break down methylmalonic acid, it builds up in the blood and causes illness. The mut methylmalonic acidemia mma caused by the deficiency of methylmalonylcoa. Methylmalonic acidemia cbl a,b information for health professionals. I dont think that methylmalonic acidemia is a disorder affecting branchedchain amino acids. Association of methylmalonic acidemia and erythema nodosum. Pdf isolated methylmalonic acidemiaaciduria is caused by complete or partial deficiency of the enzyme methylmalonylcoa mutase.
Methylmalonic acidemia with homocystinuria genetic and. Methylmalonic acidemiapropionic acidemia organic acidemia. Two of them mut0 and mut reflect deficiencies of the apoenzyme portion of the enzyme methylmalonylcoa mutase. Methylmalonic aciduria mmauria, caused by deficiency of methylmalonylcoa. Among 20 patients with mut mma, 14 had clinical presentations, and 12 presented in the neonatal period. Methylmalonic coenzyme a mutase is a vitamin b 12dependent enzyme involved in the catabolism of leucine, isoleucine, and valine. We report the case of a patient with an optic neuropathy induced by neurotoxicity in the setting of methylmalonic acidemia. 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. A modified 1cpropionate breath test was administered to 57 methylmalonic acidemia mma subjects, including 19 transplant recipients, and 16 healthy volunteers.
Methylmalonic acidemia, cobalamin c type, presenting with. A 5yearold boy presented with recurrent episodes of fever, feeding problems, lethargy, from the age of 11 months, and poor weight gain. Propionic acidemia pa and methylmalonic acidemia mma comprise the most common organic acidemias and account for profound morbidity in affected individuals. The main treatment was a lowprotein diet supplemented with lcarnitine and special milk free of leucine. Two unrelated cases of a new syndrome are now des cribed with a congenital metabolic acidosis resulting from a block in the conversion of methylmalonic acid to. Find powerpoint presentations and slides using the power of, find free presentations research about methylmalonic acidemia ppt.
He was admitted and evaluated for metabolic causes and diagnosed as having methylmalonic acidemia mma. Although liver transplantation lt has emerged as a bulk enzyme. Methylmalonic and propionic acidemia mmapa are inborn errors of metabolism characterized by accumulation of propionic acid andor methylmalonic acid. Most patients with isolated methylmalonic acidemia mma propionic acidemia pa. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to lifethreatening. 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. This study examined 12 patients with mma and eight with pa. Methylmalonic aciduria mma and propionic aciduria pa are inborn errors in the catabolism of branchedchain amino acids. Clinical picture and treatment effects in 5 patients with.
Methylmalonic acidemia genetic and rare diseases information. Neurocognitive phenotype of isolated methylmalonic acidemia. 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. These autosomal recessive disorders result from deficient activity of methylmalonyl. In some, the dermatitis is a manifestation of untreated disease, while in others, including methylmalonic acidemia, skin lesions have been ascribed to nutritional deficiency due to therapeutic amino acid restrictions. 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 with novel mut gene mutations. Methylmalonic acidemia is a genetic disease that appears in early infancy with a frequency of about 1.
Nutritional management and biochemical outcomes during. Proposed guidelines for the diagnosis and management of. Pdf treatment of methylmalonic acidemia by liver or. Mma is caused by deficiency of the mitochondrial enzyme. Because of secondary inhibition of propionylcoa carboxylase, propionic acid also accumulates, as do other organic acids. Methylmalonic acidemia cbl a,b kansas department of. Individuals with methylmalonic acidemia can be divided into two groups. On stratification by type of disorders leading to methylmalonic acidurias, 922% had methylmalonic acidemia, 1229% had cobalamin. Diagnosis and treatment of isolated methylmalonic acidemia. The clinical characteristics, laboratory findings, treatment and outcome of 40 patients were retrospectively analyzed. Isolated methylmalonic acidemia aciduria mma is a devastating metabolic disorder with poor outcomes despite current medical treatments. Mma concentrations increase when vitamin b12 is deficient.
Normally, it is quickly changed by the body into other substances. Methylmalonic acidemia mma alternate names methylmalonic aciduria methylmalonylcoa mutase deficiency mcm deficiency analytes tested c3 methodology tandem mass spectrometry tdh requisition form ph1582 form requests. Two of them mut0 and mut reflect deficiencies of the. Causes of and diagnostic approach to methylmalonic acidurias. Excess methylmalonic acid is found in the blood of people with methylmalonic acidemia. A new lcmsms method for methylmalonic acid mma analysis was developed that provides complete chromatographic resolution from isobaric succinic acid in plasma samples. Hello fellow wikipedians, i have just modified 2 external links on methylmalonic acidemia. Review open access proposed guidelines for the diagnosis. In addition methylmalonic acidemia can be caused by cobalamin disorders a and b, or methylmalonic acidemia with homocystinuria. Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. Novel mouse models of methylmalonic aciduria recapitulate.
Isolated methylmalonic acidemia aciduria is caused by complete or partial. Here, we report on a patient with methylmalonic aciduria mma who developed chronic pancreatitis after several episodes of acute pancreatitis. Excellent chromatographic results were obtained from the direct injection of a protein crash sample supernatant onto a force c18 column, providing a much simpler sample preparation compared to typical methods. Mutation analysis, treatment and prenatal diagnosis of chinese.
Methylmalonic acidemiamut information for health professionals. Anesthetic management of a patient with methylmalonic. Affected infants can experience vomiting, dehydration, weak muscle tone hypotonia, developmental. Methylmalonic acidemia with emergency hypertension nefrologia. This study aimed to identify mutations in chinese mma cases. View and download powerpoint presentations on methylmalonic acidemia ppt.
Methylmalonic acidemia mma is a heterogeneous disorder of propionate metabolism. Renal growth in isolated methylmalonic acidemia genetics. Methylmalonic aciduria, mma, isolated methylmalonic acidemia. Methylmalonic acidemia caused by methylmalonylcoa mutase deficiency is just one type of mma. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for methylmalonic acidemia.
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