A recent case report published in Molecular Genetics and Metabolism Reports describes a newborn diagnosed with DGUOK deficiency who presented with cholestasis and mildly elevated lactate levels.
Like thymidine kinase 2 deficiency (TK2d), DGUOK deficiency is a rare disease that causes defects in mitochondrial DNA maintenance. The disease often occurs in newborns and infants, with initial symptoms commonly related to liver dysfunction.
The patient, a girl born at 36 weeks and one day gestation, had two aunts who died due to liver disease during childhood. At birth, her muscle tone was normal, and she showed no signs of respiratory distress. Due to low birth weight, though, she was admitted to the hospital.
Blood testing showed increased gamma-glutamyl transferase levels, indicative of liver damage. However, ultrasound demonstrated no signs of hepatobiliary abnormalities. On day 12, the patient developed elevated bilirubin and total bile acid levels. Liver biopsy later revealed cholestasis, a condition marked by decreased bile flow from the liver.
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The patient received fat-soluble vitamins and ursodeoxycholic acid, and she switched to medium-chain triglyceride formula. Even with treatment, lactate and liver transaminase levels rose progressively. She also had an elevated lactate:pyruvate ratio, a sign of impaired mitochondrial function.
On day 64, the authors initiated a mitochondrial cocktail consisting of numerous supplements to support energy production. After four days, she developed a fever and worsening lactic acid buildup. She was ineligible for liver transplant due to poor cardiac and neurological health.
The patient began treatment with taurine and 5-aminolevulinic acid to promote metabolic function, but she died at 89 days of age due to multiple organ failure.
Postmortem analysis uncovered a pathogenic mutation in the DGUOK gene. Both parents were found to carry one copy of the gene, confirming parental inheritance.
The combination of only mildly elevated lactate levels at initial presentation and liver involvement complicated the diagnostic process, resulting in delayed diagnosis.
“Although the prognosis remains poor, early diagnosis and consideration of liver transplantation before neurological symptoms develop may improve outcomes in selected patients,” the authors concluded.
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