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References OMIM Gene GeneReviews HGMD HGNC
last update : 15-10-2013
Symbol MDDS1
Location 2p13
Name mitochondrial DNA depletion syndrome, hepatocerebral form
Other name(s)
  • mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
  • Corresponding gene DGUOK
    Other symbol(s) MTDPS3
    Main clinical features
  • hepatocerebral disease and combined respiratory chain deficiencies, muscle weakness, hepatic failure, renal tubulopathy and early death
  • liver dysfunction at birth or within a few months, with or without neurological impairment, and most die before 4 years of age due to liver failure
  • associated or not with secondary cystathioninuria
  • Genetic determination autosomal recessive
    Function/system disorder kidney and urinary tract
    digestive tract/liver and annex
    Type disease
    Gene product
    Name deoxyguanosine kinase
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function N46S and L266R in a child
    missense   abnormal protein/loss of function homozygous mutations, G352A and C269T
    Remark(s) Thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) are the two key enzymes in mitochondrial DNA (mtDNA) precursor synthesis. Deficiencies in TK2 or dGK activity, due to genetic alteration, have been shown to cause tissue-specific depletion of mtDNA. Hepatocerebral form of MDDS can also be caused by MPV17 mutations
    Genotype/Phenotype correlations with residual activity of mitochondrial enzymes