Peer-reviewed article
<i>DGUOK</i>-related mitochondrial DNA depletion syndrome presenting with neonatal cholestasis without marked hyperlactatemia: A diagnostic pitfall.
Li M, Sasai H, Taniguchi H, Ishida A, Kuwabara Y et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical case report describing a single infant with a rare genetic mitochondrial disorder (DGUOK-related mitochondrial DNA depletion syndrome) that caused liver failure in the neonatal period. The report documents the clinical presentation, diagnostic challenges, and poor outcome of this individual case. It is not a study of child well-being, health outcomes, or interventions relevant to child welfare or development.
Key points
- The case describes a premature female infant who developed neonatal cholestasis and failure to thrive
- The child died of multiple organ failure on day 89 of life
- Hyperlactatemia was absent at presentation, which delayed diagnosis
- Genetic testing revealed a homozygous variant in the DGUOK gene
- The report recommends early genetic testing for infants with unexplained cholestasis regardless of lactate levels
Limitations
This is a single clinical case report with no comparative data, population-level findings, or intervention evaluation. It cannot provide evidence about prevalence, treatment effectiveness, or outcomes across populations of children.
Abstract
Mitochondrial DNA depletion syndrome (MTDPS) is a group of severe mitochondrial disorders caused by nuclear gene variants that affect mitochondrial DNA (mtDNA) replication and nucleotide synthesis. Deoxyguanosine kinase deficiency is one of the most common subtypes, typically presenting with liver dysfunction in infancy and having a poor prognosis. We report a case of MTDPS presenting with cholestasis and mild hyperlactatemia in the neonatal period, which complicated early diagnosis. Histopathological and genetic analyses established the diagnosis. The patient, a female born at 36 weeks and 1 day of gestation, weighing 2124 g, developed cholestasis, poor feeding, and failure to thrive. Hyperlactatemia was not evident at presentation but gradually increased during the clinical course. Based on suspected mitochondrial disease, mitochondrial cocktail therapy was initiated on day 64. Liver transplantation was not feasible owing to cardiac and neurological complications, and conservative treatment was continued. However, the patient died of multiple organ failure on day 89. Postmortem liver biopsy showed a markedly reduced mtDNA copy number (8.1% of control), and genetic testing revealed a homozygous c.609_610del (p.Tyr204fs) variant in the DGUOK gene (NM_080916.3), confirming the diagnosis of DGUOK-related MTDPS. This case highlights that hyperlactatemia may be absent or only mild in the early stages of MTDPS, making timely diagnosis challenging. Mitochondrial functional analysis and genetic testing should be considered early in infants with unexplained cholestasis and liver failure, regardless of the lactate levels.