Another case of UQCRC2-related mitochondrial disease: a novel variant with atypical onset
2Hereditary Metabolic and Muscular Disorders Unit, IRCCS Anna Meyer Children Hospital, Italy
Background
We present a case of UQCRC2-related mitochondrial disease, a rare condition of defective mitochondrial respiratory chain complex III activity, usually with typical neonatal onset.
Case Study
The patient was an Italian male with a history of speech delay. He was admitted to the intensive care unit for two episodes of encephalopathy and metabolic decompensation caused by hypoalimentation and vomiting during gastrointestinal infection, at the age of 6 and 8 years old, respectively.
During the two episodes laboratory examinations showed coagulopathy, metabolic acidosis with hyperlactacidemia, hyperammoniemia and normal glycaemia. Urinary orotic acid and plasma acylcarnitines were normal, while urine organic acids showed high lactic acid and 3-hydroxy butyric acid. Plasma amino acids showed high levels of glutamine, alanine and lysine. The first episode was treated with intravenous dextrose and specific treatment for hyperammonemia, the second one required only intravenous dextrose. No sequelae were observed after both episodes.
Results
NGS-panel for acute liver failure-related genes identified a heterozygous c.379C>T (R127W) variant in UQCRC2, classified as a variant of uncertain significance, and a heterozygous 800-kb chromosome 16 deletion associated to 16p12.2 microdeletion syndrome, including UQCRC2 gene.
Conclusion
The association of UQCRC2 point mutation and microdeletion involving the same gene with an apparent homozygosity and the clinical picture leads us to believe that this variant could be pathogenic. This case emphasizes the importance of keep in mind this mitochondrial disease in patients with liver failure, hyperammoniemic encephalopathy and laboratory findings suggestive of mitochondrial disorder, even in childhood.
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