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Yin, N. Deoxyguanosine Kinase Deficiency. Encyclopedia. Available online: https://encyclopedia.pub/entry/5312 (accessed on 29 February 2024).
Yin N. Deoxyguanosine Kinase Deficiency. Encyclopedia. Available at: https://encyclopedia.pub/entry/5312. Accessed February 29, 2024.
Yin, Nicole. "Deoxyguanosine Kinase Deficiency" Encyclopedia, https://encyclopedia.pub/entry/5312 (accessed February 29, 2024).
Yin, N. (2020, December 24). Deoxyguanosine Kinase Deficiency. In Encyclopedia. https://encyclopedia.pub/entry/5312
Yin, Nicole. "Deoxyguanosine Kinase Deficiency." Encyclopedia. Web. 24 December, 2020.
Deoxyguanosine Kinase Deficiency
Edit

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.

genetic conditions

1. Introduction

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.

2. Frequency

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

3. Causes

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.

4. Inheritance

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.

5. Other Names for This Condition

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

References

  1. Alberio S, Mineri R, Tiranti V, Zeviani M. Depletion of mtDNA: syndromes andgenes. Mitochondrion. 2007 Feb-Apr;7(1-2):6-12.
  2. 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 DGUOKmutation associated with hepatocerebral mitochondrial DNA depletion syndrome. MolGenet Metab. 2009 Jul;97(3):221-6. doi: 10.1016/j.ymgme.2009.03.007.
  3. Copeland WC. Inherited mitochondrial diseases of DNA replication. Annu RevMed. 2008;59:131-46. Review.
  4. Dimmock DP, Dunn JK, Feigenbaum A, Rupar A, Horvath R, Freisinger P, Moussonde Camaret B, Wong LJ, Scaglia F. Abnormal neurological features predict poorsurvival and should preclude liver transplantation in patients withdeoxyguanosine kinase deficiency. Liver Transpl. 2008 Oct;14(10):1480-5. doi:10.1002/lt.21556.
  5. 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 tomutations in deoxyguanosine kinase. Hum Mutat. 2008 Feb;29(2):330-1. doi:10.1002/humu.9519.
  6. El-Hattab AW, Scaglia F, Wong LJ. Deoxyguanosine Kinase Deficiency. 2009 Jun18 [updated 2016 Dec 22]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, BeanLJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA):University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK7040/
  7. Freisinger P, Fütterer N, Lankes E, Gempel K, Berger TM, Spalinger J, HoerbeA, Schwantes C, Lindner M, Santer R, Burdelski M, Schaefer H, Setzer B, WalkerUA, Horváth R. Hepatocerebral mitochondrial DNA depletion syndrome caused bydeoxyguanosine kinase (DGUOK) mutations. Arch Neurol. 2006 Aug;63(8):1129-34.
  8. Labarthe F, Dobbelaere D, Devisme L, De Muret A, Jardel C, Taanman JW,Gottrand F, Lombès A. Clinical, biochemical and morphological features ofhepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosinekinase deficiency. J Hepatol. 2005 Aug;43(2):333-41.
  9. 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 kinasegene 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.
  10. 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 ofmutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.Biochem J. 2007 Mar 1;402(2):377-85.
  11. Saada-Reisch A. Deoxyribonucleoside kinases in mitochondrial DNA depletion.Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1205-15. Review.
  12. Shieh JT, Berquist WE, Zhang Q, Chou PC, Wong LJ, Enns GM. Noveldeoxyguanosine kinase gene mutations and viral infection predispose apparentlyhealthy children to fulminant liver failure. J Pediatr Gastroenterol Nutr. 2009Jul;49(1):130-2. doi: 10.1097/MPG.0b013e31819de7a6.
  13. 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 kinasemutations and combined deficiencies of the mitochondrial respiratory chain inpatients with hepatic involvement. Mol Genet Metab. 2005 Dec;86(4):462-5.
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