[MIM 251 880]

(MTDPS3, acronym for MiTochondrial DNA DePletion Syndrome-3)

Prevalence: < 1/106. Mitochondrial cytopathy due to mitochondrial DNA depletion. Autosomal recessive transmission of a mutation of the DGUOK gene (2p13.1) coding for the mitochondrial deoxyguanosine kinase involved in mitochondrial nucleotide synthesis and mitochondrial DNA replication. This leads to insufficient production of the main subunits of the mitochondrial respiratory chain complexes (factors I, III, IV, and V), resulting in insufficient energy production.

Two clinical presentations can be distinguished:

-        multi-organ disease, or hepatocerebral disease, in the first week of life with hypoglycemia and lactic acidosis, followed by hepatic dysfunction (intrahepatic cholestasis, hepatomegaly, hyperferritinemia) and neuromuscular dysfunction (hypotonia, rotary nystagmus followed by opsoclonus) in the weeks following birth. Liver dysfunction frequently progresses to neonatal or infantile liver failure with coagulopathy, ascites and edema. Biopsy: hepatic steatosis and cholestasis. Death usually before 2 years of age.

-        in a minority of cases, isolated liver disease appearing in early childhood, sometimes revealed by a viral infection. Mild hypotonia and renal impairment may be observed.

-        risk of early hepatocarcinoma (infancy)

Curative treatment: liver transplantation is reserved for cases where the disease is predominantly hepatic.

Anesthetic implications:

see mitochondrial cytopathies

References : 

-         Waich S, Roscher A, Brunner-Krainz M, Cortina G, Köstl G, Feichtinger RG, Entenmann A, Müller T, Knisely AS, Mayr JA, Janecke AR, Vodopiutz J. Severe
Deoxyguanosine Kinase Deficiency in Austria: a 6-patient series.
J Pediatr Gastroenterol Nutr 1019 ; 68 : e1-e6.

-        Duong JT, Pacheco MC, Hsu E, Blondet N.
Considerations for liver transplantation in deoxyguanosine kinase deficiency: A case series and review of the literature.
Pediatr Transplant 2024; 28 :e14670

-        Ramboux A. Poncelet A, Clapuyt P, Scheers I, Sokal E, Reding R, Stephenne X.
Deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax: a case report.
Journal of Medical Case Reports 2023 ; 17:413

Updated: March 2024