Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome.


:The causes of Reye-like syndrome are not completely understood. Dihydrolipoamide dehydrogenase (DLD or E3) deficiency is a rare metabolic disorder causing neurological or liver impairment. Specific changes in the levels of urinary and plasma metabolites are the hallmark of the classical form of the disease. Here, we report a consanguineous family of Algerian origin with DLD deficiency presenting without suggestive clinical laboratory and anatomopathological findings. Two children died at birth from hepatic failure and three currently adult siblings had recurrent episodes of hepatic cytolysis associated with liver failure or Reye-like syndrome from infancy. Biochemical investigation (lactate, pyruvate, aminoacids in plasma, organic acids in urine) was normal. Histologic examination of liver and muscle showed mild lipid inclusions that were only visible by electron microscopy. The diagnosis of DLD deficiency was possible only after genome-wide linkage analysis, confirmed by a homozygous mutation (p.G229C) in the DLD gene, previously reported in patients with the same geographic origin. DLD and pyruvate dehydrogenase activities were respectively reduced to 25% and 70% in skin fibroblasts of patients and were unresponsive to riboflavin supplementation. In conclusion, this observation clearly supports the view that DLD deficiency should be considered in patients with Reye-like syndrome or liver failure even in the absence of suggestive biochemical findings, with the p.G229C mutation screening as a valuable test in the Arab patients because of its high frequency. It also highlights the usefulness of genome-wide linkage analysis for decisive diagnosis advance in inherited metabolic disorders.


Mol Genet Metab


Brassier A,Ottolenghi C,Boutron A,Bertrand AM,Valmary-Degano S,Cervoni JP,Chrétien D,Arnoux JB,Hubert L,Rabier D,Lacaille F,de Keyzer Y,Di Martino V,de Lonlay P




Has Abstract


2013-05-01 00:00:00














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    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Jurecka A,Piotrowska E,Cimbalistiene L,Gusina N,Sobczyńska A,Czartoryska B,Czerska K,Õunap K,Węgrzyn G,Tylki-Szymańska A

    更新日期:2012-02-01 00:00:00

  • Lysosomal acid lipase mutations that determine phenotype in Wolman and cholesterol ester storage disease.

    abstract::Mechanisms producing the divergent phenotypes, Wolman disease (WD) and cholesterol ester storage disease (CESD), associated with the genetic deficiency of human lysosomal acid lipase/cholesterol ester hydrolase (hLAL) function were investigated with the determination of HLAL activity levels, mRNA and protein expressio...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


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    更新日期:1999-11-01 00:00:00

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    pub_type: 杂志文章


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    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Goldin E

    更新日期:2010-12-01 00:00:00

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    pub_type: 临床试验,杂志文章,多中心研究


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    pub_type: 杂志文章,评审


    authors: Suopanki J,Partanen S,Ezaki J,Baumann M,Kominami E,Tyynelä J

    更新日期:2000-09-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2017-03-01 00:00:00

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    authors: Komen JC,Duran M,Wanders RJ

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    pub_type: 杂志文章


    authors: Benayoun L,Granot E,Rizel L,Allon-Shalev S,Behar DM,Ben-Yosef T

    更新日期:2007-04-01 00:00:00

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    更新日期:2011-09-01 00:00:00

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    更新日期:2016-02-01 00:00:00

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    authors: Silao CL,Padilla CD,Matsuo M

    更新日期:2004-02-01 00:00:00

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    pub_type: 杂志文章,随机对照试验


    authors: Gokmen-Ozel H,Ferguson C,Evans S,Daly A,MacDonald A

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    authors: Okumiya T,Keulemans JL,Kroos MA,Van der Beek NM,Boer MA,Takeuchi H,Van Diggelen OP,Reuser AJ

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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章


    authors: Forni S,Fu X,Palmer SE,Sweetman L

    更新日期:2010-09-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2004-11-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Katz DA

    更新日期:2002-09-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Lawrence R,Brown JR,Lorey F,Dickson PI,Crawford BE,Esko JD

    更新日期:2014-02-01 00:00:00

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    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Zachor DA,Moore JF,Jin J,Theibert AB,Percy AK

    更新日期:1998-05-01 00:00:00

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    pub_type: 临床试验,杂志文章


    authors: Osher E,Fattal-Valevski A,Sagie L,Urshanski N,Amir-Levi Y,Katzburg S,Peleg L,Lerman-Sagie T,Zimran A,Elstein D,Navon R,Stern N,Valevski A

    更新日期:2011-03-01 00:00:00

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    pub_type: 杂志文章


    authors: Gaeta M,Barca E,Ruggeri P,Minutoli F,Rodolico C,Mazziotti S,Milardi D,Musumeci O,Toscano A

    更新日期:2013-11-01 00:00:00

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    pub_type: 杂志文章


    authors: Smith EH,Thomas C,McHugh D,Gavrilov D,Raymond K,Rinaldo P,Tortorelli S,Matern D,Highsmith WE,Oglesbee D

    更新日期:2010-07-01 00:00:00

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    pub_type: 杂志文章


    authors: Roberts AL,Fletcher JM,Moore L,Byers S

    更新日期:2010-10-01 00:00:00

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    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Zhang S,Li FY,Bass HN,Pursley A,Schmitt ES,Brown BL,Brundage EK,Mardach R,Wong LJ

    更新日期:2010-01-01 00:00:00