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Disease Report for: MEGDEL syndrome

Alternative name(s)|3-methylglutaconic aciduria, Type VI; MGCA6
3-methylglutaconic aciduria with deafness encephalopathy, and Leigh-like syndrome; MEGDEL
oligosystemic juvenile-onset complex hereditary spastic paraplegia (cHSP)
Mutation|27 mutations (e.g. : 1167delTCAG_human-SERAC1, D224G_human-SERAC1, G401D_human-SERAC1... more)
OMIM: |614739, 614725

Recessive disorder of dystonia and deafness with encephalopathy and Leigh-like syndrome, impaired oxidative phosphorylation and 3-methylglutaconic aciduria. Clinical features included psychomotor retardation, recurrent infections in infancy, hypoglycemia, spasticity, dystonia, sensorineural deafness, brain atrophy, and lesions on brain imaging. Laboratory studies showed increased serum lactate and alanine, urinary 3-MGA, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, an abnormal phosphatidylglycerol and cardiolipin spectrum in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells. Mutation of SERAC1 also associated with oligosystemic juvenile-onset complex hereditary spastic paraplegia (cHSP)

    Title: A novel mutation in the SERAC1 gene correlates with the severe manifestation of the MEGDEL phenotype, as revealed by whole-exome sequencing
    Alagoz M, Kherad N, Turkmen S, Bulut H, Yuksel A
    Ref: Exp Ther Med, 19:3505, 2020 : PubMed


    Title: Novel mutations in SERAC1 gene in two Indian patients presenting with dystonia and intellectual disability
    Radha Rama Devi A, Lingappa L
    Ref: Eur Journal of Medical Genetics, 61:100, 2018 : PubMed


    Title: SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family
    Roeben B, Schule R, Ruf S, Bender B, Alhaddad B, Benkert T, Meitinger T, Reich S, Bohringer J and Synofzik M <7 more author(s)>
    Ref: Journal of Medical Genetics, 55:39, 2018 : PubMed


    Title: [MEGDEL syndrome with an SERAC1 mutation: a case report]
    Chen J, Peng J, Yin F
    Ref: Zhonghua Er Ke Za Zhi, 55:394, 2017 : PubMed


    Title: MEGDEL Syndrome: Expanding the Phenotype and New Mutations
    Sequeira S, Rodrigues M, Jacinto S, Wevers RA, Wortmann SB
    Ref: Neuropediatrics, 48:382, 2017 : PubMed


    Title: Rapid Resolution of Blended or Composite Multigenic Disease in Infants by Whole-Exome Sequencing
    Theunissen TE, Sallevelt SC, Hellebrekers DM, de Koning B, Hendrickx AT, van den Bosch BJ, Kamps R, Schoonderwoerd K, Szklarczyk R and Smeets HJ <2 more author(s)>
    Ref: J Pediatr, 182:371, 2017 : PubMed


    Title: Diagnosis and Management of Drooling in Children With Progressive Dystonia: A Case Series of Patients With MEGDEL Syndrome
    Blommaert D, van Hulst K, Hoogen FJ, Erasmus CE, Wortmann SB
    Ref: Journal of Child Neurology, 31:1220, 2016 : PubMed


    Title: The clinical syndrome of dystonia with anarthria/aphonia
    Ganos C, Crowe B, Stamelou M, Kresojevic N, Lukic MJ, Bras J, Guerreiro R, Taiwo F, Balint B and Bhatia KP <6 more author(s)>
    Ref: Parkinsonism Relat Disord, 24:20, 2016 : PubMed


    Title: Transient neonatal renal failure and massive polyuria in MEGDEL syndrome
    Harbulot C, Paquay S, Dorboz I, Pichard S, Bourillon A, Benoist JF, Jardel C, Ogier de Baulny H, Boespflug-Tanguy O, Schiff M
    Ref: Mol Genet Metab Rep, 7:8, 2016 : PubMed


    Title: New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre
    Pronicka E, Piekutowska-Abramczuk D, Ciara E, Trubicka J, Rokicki D, Karkucinska-Wieckowska A, Pajdowska M, Jurkiewicz E, Halat P and Ploski R <6 more author(s)>
    Ref: J Transl Med, 14:174, 2016 : PubMed


    Title: First missense mutation outside of SERAC1 lipase domain affecting intracellular cholesterol trafficking
    Rodriguez-Garcia ME, Martin-Hernandez E, de Aragon AM, Garcia-Silva MT, Quijada-Fraile P, Arenas J, Martin MA, Martinez-Azorin F
    Ref: Neurogenetics, 17:51, 2016 : PubMed


    Title: MEGDEL Syndrome in a Child From Palestine: Report of a Novel Mutation in SERAC1 Gene
    Dweikat IM, Abdelrazeq S, Ayesh S, Jundi T
    Ref: Journal of Child Neurology, 30:1053, 2015 : PubMed


    Title: Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation
    Unal O, Ozgul RK, Yucel D, Yalnizoglu D, Tokatli A, Sivri HS, Hismi B, Coskun T, Dursun A
    Ref: Turk J Pediatr, 57:388, 2015 : PubMed


    Title: Tubular aggregates caused by serine active site containing 1 (SERAC1) mutations in a patient with a mitochondrial encephalopathy
    Wedatilake Y, Plagnol V, Anderson G, Paine SM, Clayton PT, Jacques TS, Rahman S
    Ref: Neuropathol Appl Neurobiol, 41:399, 2015 : PubMed


    Title: Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome
    Wortmann SB, van Hasselt PM, Baric I, Burlina A, Darin N, Horster F, Coker M, Ucar SK, Krumina Z and Willemsen MA <15 more author(s)>
    Ref: Neuropediatrics, 46:98, 2015 : PubMed


    Title: The Expanding MEGDEL Phenotype: Optic Nerve Atrophy, Microcephaly, and Myoclonic Epilepsy in a Child with SERAC1 Mutations
    Lumish HS, Yang Y, Xia F, Wilson A, Chung WK
    Ref: JIMD Rep, 16:75, 2014 : PubMed


    Title: Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1
    Sarig O, Goldsher D, Nousbeck J, Fuchs-Telem D, Cohen-Katsenelson K, Iancu TC, Manov I, Saada A, Sprecher E, Mandel H
    Ref: American Journal of Medicine Genet A, 161A:2204, 2013 : PubMed


    Title: Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria
    Tort F, Garcia-Silva MT, Ferrer-Cortes X, Navarro-Sastre A, Garcia-Villoria J, Coll MJ, Vidal E, Jimenez-Almazan J, Dopazo J and Ribes A <2 more author(s)>
    Ref: Mol Genet Metab, 110:73, 2013 : PubMed


    Title: Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature
    Wortmann SB, Duran M, Anikster Y, Barth PG, Sperl W, Zschocke J, Morava E, Wevers RA
    Ref: J Inherit Metab Dis, 36:923, 2013 : PubMed


    Title: Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness
    Wortmann SB, Vaz FM, Gardeitchik T, Vissers LE, Renkema GH, Schuurs-Hoeijmakers JH, Kulik W, Lammens M, Christin C and de Brouwer AP <24 more author(s)>
    Ref: Nat Genet, 44:797, 2012 : PubMed


    Title: Increased reactive oxygen species (ROS) production and low catalase level in fibroblasts of a girl with MEGDEL association (Leigh syndrome, deafness, 3-methylglutaconic aciduria)
    Karkucinska-Wieckowska A, Lebiedzinska M, Jurkiewicz E, Pajdowska M, Trubicka J, Szymanska-Debinska T, Suski J, Pinton P, Duszynski J and Pronicka E <2 more author(s)>
    Ref: Folia Neuropathol, 49:56, 2011 : PubMed


    Title: Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation
    Wortmann S, Rodenburg RJ, Huizing M, Loupatty FJ, de Koning T, Kluijtmans LA, Engelke U, Wevers R, Smeitink JA, Morava E
    Ref: Mol Genet Metab, 88:47, 2006 : PubMed


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Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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