Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain

Eilon Shany, Ann Saada, Daniella Landau, Avraham Shaag, Eli Hershkovitz, Orly N. Elpeleg

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

An infant with a neurodegenerative disorder accompanied by lactic acidemia is described. In muscle homogenate, the activity of lipoamide dehydrogenase (LAD), the third catalytic subunit of pyruvate dehydrogenase complex (PDHc), α-ketoglutarate dehydrogenase complex (KGDHc), and branched-chain keto acid dehydrogenase complex was reduced to 15% of the control. The activity of PDHc was undetectable and the activity of KGDHc was 2% of the control mean. The immunoreactive LAD protein was reduced to about 10% of the control. Direct sequencing of LAD cDNA revealed only one mutation, substituting Asp for Val at position 479 of the precursor form. The mutation resides within the interface domain and likely perturbs stable dimerization. The phenotypic heterogeneity in LAD deficiency is not directly correlated with the residual LAD activity but rather with its impact on the multienzymatic complex activity.

Original languageEnglish
Pages (from-to)163-166
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume262
Issue number1
DOIs
StatePublished - 19 Aug 1999
Externally publishedYes

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