Investigation of mitochondrial DNA depletion syndromes in children under 5 years old with acute liver manifestations of unknown etiology
2Intergen Genetic Diagnosis and Research Center, Turkiye
3Ankara Yildirim Beyazit University, Ankara City Hospital, Department of Pediatric Metabolism, Turkiye
4Manisa City Hospital, Department of Pediatric Metabolism, Turkiye
Background: Acute liver disease in children is rare and can be fatal if left untreated. The etiology is important for the treatment and the prognosis. Mitochondrial diseases can occur in all age groups and can progress with liver failure. In this study, we aim to determine the frequency of mitochondrial DNA depletion syndromes (MDDS) in patients under 5 years of age who presented with acute liver manifestations.
Methods: Patients under the age of 5 who presented with acute liver manifestations and were consulted to the Pediatric Metabolic Diseases department for inherited metabolic diseases, in whom other etiological causes were excluded and the diagnosis could not be determined were included. Genes associated with MDDS (DGUOK, FBXL4, MGME1, MPV17, OPA1, POLG, RRM2B, SLC25A4, SUCLA2, SUCLG1, TFAM, TK2, TWNK, TYMP) were analyzed in patients included in the study. Demographic, clinical, laboratory and imaging data and genetic results of the patients were evaluated together.
Results: Forty-one patients were included in the study. Twenty-one (51.2%) of the patients were male. The median age of the patients was 260.8(1-1760) days. Parental consanguinity was present in 27(65.9%) patients. The clinical and laboratory findings revealed that all patients (100%) had transaminase elevation, 31 (75.6%) cholestasis, 31 (75.6%) increased INR, 25(61%) lactate elavation, 28(68.3%) hepatomegaly, and 10(24.4%) splenomegaly.
MDDS was diagnosed in 9 of the patients (Figure 1). While 5(12.2%) of them were diagnosed as DGUOK, 2(4.9%) as TWNK, one as MPV17 and one as POLG. While all patients diagnosed with MDDS had elevated lactate, 50% of patients without MDDS had elevated lactate (p=0.007). All patients diagnosed with MDDS had a history of parental consanguinity, while the rate of parental consanguinity was 56.3% in those without MDDS (p=0.017). Similar family history was present in 5(55.6%) of the patients with MDDS and 5(15.6%) of the patients without MDDS (p=0.025).
Discussion/Conclusion: In our study, the incidence of MDDS was found to be 21.9% in pediatric patients who presented with acute liver manifestations. It should be kept in mind that MDDS may also be seen in pediatric cases presenting with acute liver manifestations.
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