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Deoxyguanosine kinase deficiency

Reviewed December 2009

What is deoxyguanosine kinase deficiency?

Deoxyguanosine kinase deficiency is an inherited disorder that can cause liver disease and neurological problems. Researchers have described two forms of this disorder. The majority of affected individuals have the more severe form, which is called hepatocerebral because of the serious problems it causes in the liver and brain.

Newborns with the hepatocerebral form of deoxyguanosine kinase deficiency may have a buildup of lactic acid in the body (lactic acidosis) within the first few days after birth. They may also have weakness, behavior changes such as poor feeding and decreased activity, and vomiting. Affected newborns sometimes have low blood sugar (hypoglycemia) as a result of liver dysfunction. During the first few weeks of life they begin showing other signs of liver disease which may result in liver failure. They also develop progressive neurological problems including very weak muscle tone (severe hypotonia), abnormal eye movements (nystagmus) and the loss of skills they had previously acquired (developmental regression). Children with this form of the disorder usually do not survive past the age of 2 years.

Some individuals with deoxyguanosine kinase deficiency have a milder form of the disorder without severe neurological problems. Liver disease is the primary symptom of this form of the disorder, generally becoming evident during infancy or childhood. Occasionally it first appears after an illness such as a viral infection. Affected individuals may also develop kidney problems. Mild hypotonia is the only neurological effect associated with this form of the disorder.

How common is deoxyguanosine kinase deficiency?

The prevalence of deoxyguanosine kinase deficiency is unknown. Approximately 100 affected individuals have been identified.

What genes are related to deoxyguanosine kinase deficiency?

The DGUOK gene provides instructions for making the enzyme deoxyguanosine kinase. This enzyme plays a critical role in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the building blocks of mitochondrial DNA.

Mutations in the DGUOK gene reduce or eliminate the activity of the deoxyguanosine kinase enzyme. Reduced enzyme activity leads to problems with the production and maintenance of mitochondrial DNA. A reduction in the amount of mitochondrial DNA (known as mitochondrial DNA depletion) impairs mitochondrial function in many of the body's cells and tissues. These problems lead to the neurological and liver dysfunction associated with deoxyguanosine kinase deficiency.

Related Gene(s)

Changes in this gene are associated with deoxyguanosine kinase deficiency.

  • DGUOK

How do people inherit deoxyguanosine kinase deficiency?

Deoxyguanosine kinase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In most cases, the parents of an individual with this condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of deoxyguanosine kinase deficiency?

These resources address the diagnosis or management of deoxyguanosine kinase deficiency and may include treatment providers.

  • Gene Review: DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form (http://www.ncbi.nlm.nih.gov/books/NBK7040/)
  • Genetic Testing Registry: Mitochondrial DNA-depletion syndrome 3, hepatocerebral (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3151513)
  • MedlinePlus Encyclopedia: Hypotonia (http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm)

You might also find information on the diagnosis or management of deoxyguanosine kinase deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about deoxyguanosine kinase deficiency?

You may find the following resources about deoxyguanosine kinase deficiency helpful. These materials are written for the general public.

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

What other names do people use for deoxyguanosine kinase deficiency?

  • DGUOK-related mitochondrial DNA depletion syndrome
  • hepatocerebral mitochondrial DNA depletion syndrome
  • mitochondrial DNA depletion syndrome, hepatocerebral form

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about deoxyguanosine kinase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding deoxyguanosine kinase deficiency?

acidosis ; autosomal ; autosomal recessive ; cell ; deficiency ; depletion ; DNA ; enzyme ; gene ; hypoglycemia ; hypotonia ; infection ; kidney ; kinase ; lactic acid ; lactic acidosis ; liver failure ; mitochondria ; muscle tone ; neurological ; nystagmus ; prevalence ; recessive ; regression ; symptom ; syndrome

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

References

  • Alberio S, Mineri R, Tiranti V, Zeviani M. Depletion of mtDNA: syndromes and genes. Mitochondrion. 2007 Feb-Apr;7(1-2):6-12. Epub 2006 Dec 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17280874?dopt=Abstract)
  • Brahimi N, Jambou M, Sarzi E, Serre V, Boddaert N, Romano S, de Lonlay P, Slama A, Munnich A, Rötig A, Bonnefont JP, Lebre AS. The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome. Mol Genet Metab. 2009 Jul;97(3):221-6. doi: 10.1016/j.ymgme.2009.03.007. Epub 2009 Mar 27. (http://www.ncbi.nlm.nih.gov/pubmed/19394258?dopt=Abstract)
  • Copeland WC. Inherited mitochondrial diseases of DNA replication. Annu Rev Med. 2008;59:131-46. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17892433?dopt=Abstract)
  • Dimmock DP, Dunn JK, Feigenbaum A, Rupar A, Horvath R, Freisinger P, Mousson de Camaret B, Wong LJ, Scaglia F. Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency. Liver Transpl. 2008 Oct;14(10):1480-5. doi: 10.1002/lt.21556. (http://www.ncbi.nlm.nih.gov/pubmed/18825706?dopt=Abstract)
  • Dimmock DP, Zhang Q, Dionisi-Vici C, Carrozzo R, Shieh J, Tang LY, Truong C, Schmitt E, Sifry-Platt M, Lucioli S, Santorelli FM, Ficicioglu CH, Rodriguez M, Wierenga K, Enns GM, Longo N, Lipson MH, Vallance H, Craigen WJ, Scaglia F, Wong LJ. Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase. Hum Mutat. 2008 Feb;29(2):330-1. doi: 10.1002/humu.9519. (http://www.ncbi.nlm.nih.gov/pubmed/18205204?dopt=Abstract)
  • Freisinger P, Fütterer N, Lankes E, Gempel K, Berger TM, Spalinger J, Hoerbe A, Schwantes C, Lindner M, Santer R, Burdelski M, Schaefer H, Setzer B, Walker UA, Horváth R. Hepatocerebral mitochondrial DNA depletion syndrome caused by deoxyguanosine kinase (DGUOK) mutations. Arch Neurol. 2006 Aug;63(8):1129-34. (http://www.ncbi.nlm.nih.gov/pubmed/16908739?dopt=Abstract)
  • Gene Review: DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form (http://www.ncbi.nlm.nih.gov/books/NBK7040/)
  • Labarthe F, Dobbelaere D, Devisme L, De Muret A, Jardel C, Taanman JW, Gottrand F, Lombès A. Clinical, biochemical and morphological features of hepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosine kinase deficiency. J Hepatol. 2005 Aug;43(2):333-41. (http://www.ncbi.nlm.nih.gov/pubmed/15964659?dopt=Abstract)
  • Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, Shalata A, Anbinder Y, Berkowitz D, Hartman C, Barak M, Eriksson S, Cohen N. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet. 2001 Nov;29(3):337-41. Erratum in: Nat Genet 2001 Dec;29(4):491. (http://www.ncbi.nlm.nih.gov/pubmed/11687800?dopt=Abstract)
  • Mousson de Camaret B, Taanman JW, Padet S, Chassagne M, Mayençon M, Clerc-Renaud P, Mandon G, Zabot MT, Lachaux A, Bozon D. Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion. Biochem J. 2007 Mar 1;402(2):377-85. (http://www.ncbi.nlm.nih.gov/pubmed/17073823?dopt=Abstract)
  • Saada-Reisch A. Deoxyribonucleoside kinases in mitochondrial DNA depletion. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1205-15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15571232?dopt=Abstract)
  • Shieh JT, Berquist WE, Zhang Q, Chou PC, Wong LJ, Enns GM. Novel deoxyguanosine kinase gene mutations and viral infection predispose apparently healthy children to fulminant liver failure. J Pediatr Gastroenterol Nutr. 2009 Jul;49(1):130-2. doi: 10.1097/MPG.0b013e31819de7a6. (http://www.ncbi.nlm.nih.gov/pubmed/19502998?dopt=Abstract)
  • Slama A, Giurgea I, Debrey D, Bridoux D, de Lonlay P, Levy P, Chretien D, Brivet M, Legrand A, Rustin P, Munnich A, Rötig A. Deoxyguanosine kinase mutations and combined deficiencies of the mitochondrial respiratory chain in patients with hepatic involvement. Mol Genet Metab. 2005 Dec;86(4):462-5. Epub 2005 Nov 2. (http://www.ncbi.nlm.nih.gov/pubmed/16263314?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: December 2009
Published: April 21, 2014