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Korean J Gastroenterol < Volume 77(5); 2021 < Articles
Mitochondrial DNA (mtDNA) depletion syndrome comprises a group of diseases caused by a deficiency of proteins involved in mtDNA synthesis, leading to quantitative (mtDNA depletion) and qualitative (multiple mtDNA deletions) defects in mtDNA.1 The diseases are classified based on the organs predominantly affected, such as encephalohepatopathy, encephalomyopathy, encephaloneuropathy, neurogastrointestinal encephalopathy, myopathy, ophthalmoplegia, optic atrophy, and neuropathy.2
A 17-month-old Korean girl was admitted to Seoul National University Children Hospital to understand her developmental delay and failure to thrive. She was born as a dichorionic diamniotic twin infant to nonconsanguineous parents at 37+1 weeks of gestation with a birth weight of 2.04 kg (<3rd percentile), height of 45.6 cm (50th percentile), and head circumference of 32.0 cm (50th percentile). Immediately after birth, she was admitted to a nursery for routine neonatal care. The liver function (AST, ALT, total bilirubin) and newborn screening test results were normal.
Her vital signs were normal during admission. Her height, weight, and head circumference were 70.6 cm (<3rd percentile), 7 kg (<3rd percentile), and 41.4 cm (<3rd percentile), respectively. Her motor developmental age was 10 months, as assessed using Gross Motor Function Measure with a score of 63.07%. A physical examination revealed central hypotonia and hepatomegaly. The laboratory tests showed elevated transaminases, ALP, GGT (AST 330 U/L, ALT 150 U/L, ALP 462 U/L, GGT 81 U/L), lactic acidemia (lactic acid 4.5 mmol/L, reference range 0.8-1.5 mmol/L), hyperbilirubinemia (total bilirubin 4.7 mg/dL, reference range 0.2-1.2 mg/dL; direct bilirubin 4.18 mg/dL, reference range 0-0.5 mg/dL), and coagulopathy (PT INR 1.87, reference range 0.8-1.2). The lactic acid-to-pyruvate ratio was 45.04. The newborn screening test and serology, including hepatitis A virus, hepatitis B virus, hepatitis C virus, herpes simplex virus, Epstein-Barr virus, and cytomegalovirus, were unremarkable.
The abdominal ultrasound showed increased parenchymal echogenicity and periportal edema, and elastography revealed increased liver stiffness. Brain MRI showed extensive white matter T2-hyperintensity, suggesting a hypo-state or demyelination state (Fig. 1). Thus, the patient received fat-soluble vitamin replacement and medium-chain triglyceride supplementation. Subsequently, her total bilirubin and direct bilirubin levels decreased to 1.1 mg/dL and 1.02 mg/dL, respectively.
She was infected with adenovirus that manifested as diarrhea, vomiting, fever, and poor oral intake. She visited an emergency room because of a seizure. Her initial blood sugar level was 11 mg/dL; thus, she was fed uncooked cornstarch.
WES was performed using the genomic DNA from the peripheral leukocytes, and mutations were detected in
Although the patient exhibited developmental delay, she underwent physical therapy for eight months and showed improvement in development. Her gross motor function measure score was 86.9%, but her liver function tests were aggravated. Despite the administration of vitamin K, her serum total bilirubin level was 2.6 mg/dL (direct bilirubin level 2.27 mg/dL) and PT INR was 3.21. Subsequently, she manifested with liver failure and mild neurological symptoms and is being considered for deceased donor liver transplantation. The Institutional Review Board of Seoul National University Hospital approved this study (Approval No. 1807-137-961).
Although
The potential of WES was introduced in 2009,8,9 and has since been improved. WES is a cost-effective and useful genetic diagnostic tool.10,11 In addition to
To date, 48
Genotype-phenotype correlations caused by
Previously, several
The outcome of liver transplantation (LT) in patients with
In conclusion, this paper reported the clinical manifestations of
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