Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

DLD

Reviewed July 2012

What is the official name of the DLD gene?

The official name of this gene is “dihydrolipoamide dehydrogenase.”

DLD is the gene's official symbol. The DLD gene is also known by other names, listed below.

What is the normal function of the DLD gene?

The DLD gene provides instructions for making a protein called dihydrolipoamide dehydrogenase. This protein is a part (a subunit) of several enzyme complexes (groups of enzymes that work together). These complexes are essential for the breakdown of certain molecules to produce energy in cells. Dihydrolipoamide dehydrogenase forms a subunit called the E3 component that is shared by several enzyme complexes.

Branched-chain alpha-keto acid dehydrogenase, or BCKD, is one of the enzyme complexes that include the E3 component. The BCKD enzyme complex performs one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The breakdown of these amino acids produces molecules that can be used for energy.

The E3 component is also part of the pyruvate dehydrogenase complex. This enzyme complex plays an important role in the production of energy for cells. It converts a molecule called pyruvate, which is formed from the breakdown of carbohydrates, into another molecule called acetyl-CoA. The E3 component performs one part of this chemical reaction. The conversion of pyruvate is essential to begin the series of chemical reactions that produces adenosine triphosphate (ATP), the cell's main energy source.

How are changes in the DLD gene related to health conditions?

maple syrup urine disease - caused by mutations in the DLD gene

More than 10 mutations in the DLD gene have been identified in people with maple syrup urine disease. Mutations in this gene are responsible for a variant form of the disorder that includes lactic acidosis, a potentially life-threatening complication caused by the buildup of lactic acid in the body's tissues.

Most DLD mutations change single amino acids in the E3 component of the BCKD enzyme complex. These mutations alter the structure of the E3 component, which prevents the enzyme complex from effectively breaking down valine, isoleucine, and leucine. As a result, these amino acids and their byproducts build up in the body. This accumulation is toxic to cells and tissues, particularly in the nervous system. The buildup of these substances can lead to seizures, developmental delay, and the other health problems associated with maple syrup urine disease.

Most people with maple syrup urine disease have reduced function of the other enzyme complexes that contain the E3 enzyme, which may account for the overlapping features of this condition and pyruvate dehydrogenase deficiency (described below).

pyruvate dehydrogenase deficiency - caused by mutations in the DLD gene

Mutations in the DLD gene cause pyruvate dehydrogenase deficiency in a small number of people. This condition is characterized by lactic acidosis, delayed development, and neurological problems. Most DLD gene mutations associated with pyruvate dehydrogenase deficiency change single amino acids in the E3 component, which results in a reduction of its function. This decrease leads to a reduction of pyruvate dehydrogenase complex activity. With decreased function of this complex, pyruvate builds up and is converted, in another chemical reaction, to lactic acid, causing lactic acidosis. In addition, the production of cellular energy is diminished. The brain, which is especially dependent on this form of energy, is severely affected, resulting in the neurological problems associated with pyruvate dehydrogenase deficiency.

Most people with pyruvate dehydrogenase deficiency also have reduced function of the other enzyme complexes that contain the E3 enzyme, which may account for the overlapping features of this condition and maple syrup urine disease (described above).

Where is the DLD gene located?

Cytogenetic Location: 7q31-q32

Molecular Location on chromosome 7: base pairs 107,891,140 to 107,921,197

The DLD gene is located on the long (q) arm of chromosome 7 between positions 31 and 32.

The DLD gene is located on the long (q) arm of chromosome 7 between positions 31 and 32.

More precisely, the DLD gene is located from base pair 107,891,140 to base pair 107,921,197 on chromosome 7.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about DLD?

You and your healthcare professional may find the following resources about DLD helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the DLD gene or gene products?

  • DIA1
  • diaphorase
  • dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex)
  • dihydrolipoyl dehydrogenase
  • DLDH
  • DLDH_HUMAN
  • E3 component of pyruvate dehydrogenase
  • GCSL
  • glycine cleavage system L protein
  • LAD
  • lipoamide dehydrogenase
  • lipoamide reductase
  • lipoamide reductase (NADH)
  • lipoyl dehydrogenase
  • PHE3
  • pyruvate dehydrogenase component E3

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding DLD?

acidosis ; acids ; adenosine triphosphate ; ATP ; breakdown ; cell ; CoA ; complication ; deficiency ; dehydrogenase ; developmental delay ; enzyme ; gene ; glycine ; isoleucine ; lactic acid ; lactic acidosis ; leucine ; molecule ; nervous system ; neurological ; protein ; subunit ; toxic ; valine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Biochemistry (fifth edition, 2002): The Formation of Acetyl Coenzyme A from Pyruvate (http://www.ncbi.nlm.nih.gov/books/NBK22427/)
  • Cerna L, Wenchich L, Hansiková H, Kmoch S, Peskova K, Chrastina P, Brynda J, Zeman J. Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency. Med Sci Monit. 2001 Nov-Dec;7(6):1319-25. (http://www.ncbi.nlm.nih.gov/pubmed/11687750?dopt=Abstract)
  • Feigenbaum AS, Robinson BH. The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Genomics. 1993 Aug;17(2):376-81. (http://www.ncbi.nlm.nih.gov/pubmed/8406489?dopt=Abstract)
  • Hong YS, Kerr DS, Liu TC, Lusk M, Powell BR, Patel MS. Deficiency of dihydrolipoamide dehydrogenase due to two mutant alleles (E340K and G101del). Analysis of a family and prenatal testing. Biochim Biophys Acta. 1997 Dec 31;1362(2-3):160-8. (http://www.ncbi.nlm.nih.gov/pubmed/9540846?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1738)
  • Patel MS, Korotchkina LG, Sidhu S. Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex. J Mol Catal B Enzym. 2009 Nov 1;61(1-2):2-6. (http://www.ncbi.nlm.nih.gov/pubmed/20160912?dopt=Abstract)
  • Saada A, Aptowitzer I, Link G, Elpeleg ON. ATP synthesis in lipoamide dehydrogenase deficiency. Biochem Biophys Res Commun. 2000 Mar 16;269(2):382-6. (http://www.ncbi.nlm.nih.gov/pubmed/10708561?dopt=Abstract)
  • Shaag A, Saada A, Berger I, Mandel H, Joseph A, Feigenbaum A, Elpeleg ON. Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. Am J Med Genet. 1999 Jan 15;82(2):177-82. (http://www.ncbi.nlm.nih.gov/pubmed/9934985?dopt=Abstract)
  • Shany E, Saada A, Landau D, Shaag A, Hershkovitz E, Elpeleg ON. Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain. Biochem Biophys Res Commun. 1999 Aug 19;262(1):163-6. (http://www.ncbi.nlm.nih.gov/pubmed/10448086?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2012
Published: July 21, 2014