Connexion

GENATLAS PHENOTYPE

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
	neuromuscular
Type	disease

Gene product

Name

deoxyguanosine kinase

Mechanism(s)

Gene mutation	Effect	Comments

missense	abnormal protein/loss of function	N46S and L266R in a child
missense	abnormal protein/loss of function	homozygous mutations, G352A and C269T
other

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