Visit Metagene.de!
Summary
METHYLMALONIC ACIDURIA (MMA)
METHYLMALONACIDURIA DUE TO METHYLMALONIC COA MUTASE ACIDEMIA, METHYLMALONIC
251000
OMIM = Online Medalian Inheritance of Men
289916
6p12.3
  • amino acid mixture
  • cobalamin
  • creatine monohydrate
  • frequent feeding
  • glucose infusion (acute)
  • hemofiltration/hemodialysis/peritonealdialysis
  • kidney transplantation
  • L-carnitine
  • liver-kidney transplantation
  • low-protein diet
  • metronidazole
  • sodium bicarbonate
rare (1:20000 )
autosomal recessive
caused by mutation in the gene encoding methylmalonyl-CoA mutase (MUT)
mut0 and mut- defects, the latter with milder course
symptoms
Amino acids, urine
anemia
behavior, hyperactive, restless
cardiomyopathy
cardiomyopathy, dilated
coma
decreased body hair
dehydration
diarrhea
failure to thrive
feeding difficulties, poor feeding
growth retardation
hyperammonemia
hyperglycemia
hypothermia
hypotonia
ketosis, ketoacidosis
mental retardation
metabolic acidosis
nephrosis
neutropenia (decreased neutrophils)
onset, childhood
onset, infancy
onset, neonatal
optic atrophy
optic neuropathy
Organic acids, urine
pancreatitis
pulmonary hypertension
renal failure, acute/chronic
respiratory distress
seizures
skin defects
spastic diplegia/quadriplegia
strokelike episodes
tachypnea, hyperpnea, dyspnea, respiratory distress
thrombopenia, thrombocytopenia
vomiting
laboratory finding
Methylmalonic acid150.0015500.000.002.00mmol/mol creatinineurinenewborn
Methylcitric acid150.002800.002.0012.00mmol/mol creatinineurinenewborn
3-Hydroxypropionic acid20.002000.003.0010.00mmol/mol creatinineurine
Propionylglycine0.00450.000.002.00mmol/mol creatinineurine
3-Hydroxyvaleric acid2.001200.000.002.00mmol/mol creatinineurinechild
Glycine1000.005000.00210.00743.00mmol/mol creatinineurine
Methylmalonic acid121.00342.000.000.00-Ámol/lcerebrospinal fluid
Ammonia60.002000.0025.0080.00-Ámol/lblood
Creatinine90.00329.0027.0088.00-Ámol/lserum
pCO215.0045.0038.0042.00mm Hgblood
pH7.007.407.357.45no unitblood
Methylmalonyl CoA mutase0.0010.00 100.00% of normalfibroblasts
Uric acid 0.605.50increasedserum
Acylcarnitine0.000.00 increasedurineno data
Ketone bodies0.000.00 +/++urineno data
Carnitine 23.0060.00decreasedplasma
MRI, brain, gray matter abnormalities -
Methylmalonic acid increasedplasma
5-Oxoproline0.000.00 increasedurineno data
Propionylcarnitine (C3) increasedblood
Methylmalonylcarnitine (C4DC) increasedblood
Gaucher cells, bone marrow, spleen150.0015500.000.002.00mmol/mol creatinineurinenewborn
Biopterin150.0015500.000.002.00mmol/mol creatinineurinenewborn
Inosine150.0015500.000.002.00mmol/mol creatinineurinenewborn
Transferrin150.0015500.000.002.00mmol/mol creatinineurinenewborn
L-Tyrosine150.0015500.000.002.00mmol/mol creatinineurinenewborn
Cortisol/cortisone ratio150.0015500.000.002.00mmol/mol creatinineurinenewborn
3-Aminoisobutyric acid0.000.00 increasedurineno data
Heptadecanoylcarnitine (C17)0.000.00 increasedbloodnewborn
Literature
Ichinose Het al.Molecular genetics of dopa-responsive dystoniaBiol Chem38001355-13641999
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Wortmann SB,et al.The 3-methylglutaconic acidurias: whats new?J Inher Metab Dis35113-222012
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Clayton BEJenkins P, Round JMPaediatric chemical pathology - clinical tests and reference rangesBlackwell, Oxford001980
Sweetman LOrganic acid analysisTechniques in diagnostic human biochemical genetics: a laboratory manual Editor F.A.HommesWiley-Liss Inc. New York00143-1761991
Xiong Het al.Clinical characteristics of X-linked adrenoleukodystrophyZhonghua Er Ke Za Zhi413203-2072003
Vassault ABonnefort JP, Specola N, Saudubray LMLactate, Pyruvate, and Ketone BodiesTechniques in diagnostic human biochemical genetics: a laboratory manual Editor F.A.HommesWiley-Liss Inc. New York00285-3081991
Lissens Wet al.Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiencyHum Mutat153209-2152000
Mercimek-Mahmutoglu S,Tucker T, Casey BPhenotypic heterogeneity in two siblings with 3-methylglutaconic aciduria type I caused by a novel intragenic deletionMol Genet Metab1043410-4132011
Bjorkhem ILeitersdorf ESterol 27-hydroxylase deficiency: a rare cause of xanthomas in normocholesterolemic humansTrends Endocrinol Metab115180-1832000
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Guneral FBachmann CAge-Related Reference Values for Urinary Organic Acids in a Healthy Turkish Pediatric PopulationClin Chem406862-8681994
Wortmann SB,et al.The 3-methylglutaconic acidurias: whats new?J Inher Metab Dis35113-222012
Uchino Tet al.Three brothers with progressive hepatic dysfunction and severe hepatic steatosis due to a patent ductus venosusGastroenterology11001964-19681996
Brown RMet al.Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiencyHum Genet1152123-1272004
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Wortmann SB,et al.The 3-methylglutaconic acidurias: whats new?J Inher Metab Dis35113-222012
Pineda Met al.An atypical French form of pyruvate carboxylase deficiencyBrain Dev174276-2791995
Guneral FBachmann CAge-Related Reference Values for Urinary Organic Acids in a Healthy Turkish Pediatric PopulationClin Chem406862-8681994
Sweetman LOrganic acid analysisTechniques in diagnostic human biochemical genetics: a laboratory manual Editor F.A.HommesWiley-Liss Inc. New York00143-1761991
Gitzelmann R, Forster I, Willi UVHypergalactosaemia in a newborn: self-limiting intrahepatic portosystemic venous shuntEur J Pediatr1560719-7221997
Chaves FJet al.Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterolJ Clin Endocrinol Metab86104926-49322001
Fouque Fet al.Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiencyPediatr Res535793-7992003
Wortmann SB,et al.3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathyNeurology75121079-10832010
Brown RMHead RA, Brown GKPyruvate dehydrogenase E3 binding protein deficiencyHum Genet1102187-1972002
Ichinose Het al.Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GPT cyclohydrolase I geneNat Genet83236-2421994
Heymans HSWanders RJA, Schutgens RBHPeroxisomal disordersJ Inherit Metab Dis00421-4331995
Hoffmann GFDie Mevalonazidurie - eine Stoffwechselerkrankung der Cholesterin- und IsoprenoidbiosyntheseThieme Verlag Stuttgart New York001994
Dedoussis GVet al.LDL-receptor mutations in EuropeHum Mutat246443-4592004
Stern HJet al.Prolonged survival in pyruvate carboxylase deficiency: lack of correlation with enzyme activity in cultured fibroblastsClin Biochem28185-891995
Gitzelmann R, Arbenz UV, Willi UVHypergalactosaemia and portosystemic encephalopathy due to persistence of ductus venosus ArantiiEur J Pediatr1510564-5681992
Brusilow SWHorwich ALUrea cycle enzymesThe metabolic and molecular bases of inherited disease, 7/e Editors: C.R.Scriver, A.L.Beaudet, W.S.Sly, D.Valle McGraw-Hill Inc.101187-12321995
Boren Jet al.The molecular mechanism for the genetic disorder familial defective apolipoprotein B100J Biol Chem276129214-92182001
Mandel Het al.The hepatic mitochondrial DNA depletion syndrome: ultrastructural changes in liver biopsiesHepatology340776-7842001
Wortmann SB,et al.The 3-methylglutaconic acidurias: whats new?J Inher Metab Dis35113-222012
Rodenburg Jet al.Familial hypercholesterolemia in childrenCurr Opin Lipidol154405-4112004
Tabatabaie L,et al.Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiencyJ Inherit Metab Dis. 2011 Feb34(1):181-4. Epub 2010 Nov 27.341181-1842011
Federico ADotti MTCerebrotendinous xanthomatosis: clinical manifestations, diagnostic criteria, pathogenesis, and therapyJ Child Neurol189633-6382003
Sweetman LOrganic acid analysisTechniques in diagnostic human biochemical genetics: a laboratory manual Editor F.A.HommesWiley-Liss Inc. New York00143-1761991
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993
Head RAet al.Pyruvate dehydrogenase deficiency presenting as dystonia in childhoodDev Med Child Neurol4610710-7122004
Nyhan WLet al.Pyruvate carboxylase deficiency--insights from liver transplantationMol Genet Metab770143-1492002
Austin MAet al.Familial hypercholesterolemia and coronary heart disease: a HuGE association reviewAm J Epidemiol1605421-4292004
Houten SMet al.Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndromeNat Genet220175-1771999
Sweetman LOrganic acid analysisTechniques in diagnostic human biochemical genetics: a laboratory manual Editor F.A.HommesWiley-Liss Inc. New York00143-1761991
Vassault ABonnefort JP, Specola N, Saudubray LMLactate, Pyruvate, and Ketone BodiesTechniques in diagnostic human biochemical genetics: a laboratory manual Editor F.A.HommesWiley-Liss Inc. New York00285-3081991
Clayton BEJenkins P, Round JMPaediatric chemical pathology - clinical tests and reference rangesBlackwell, Oxford001980
Barth PGHoffmann GF, Jaeken J, Lehnert W, Hanefeld F, van Gennip AH, Duran M, Valk J, Schutgens RBH, Trefz FK, Reimann G, HartunL-2-Hydroxyglutaric acid Acidemia: A Novel Inherited Neurometabolic DiseaseAnnals of Neurology32166-711992
Hoffmann GFMeier-Augenstein W, St+Âckler S, Surtees R, Rating D, Nyhan WLPhysiology and Pathophysiology of Organic Acid in Cerebrospinal FluidJ Inherit Metab Dis160648-6691993