A patient with a RARS2 mutation exhibiting anemia as a possible new clinical feature
2Metabolic Disease, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel
3Sackler Faculty of Medicine, Tel Aviv University, Israel
Background: Pontocerebellar hypoplasia type 6 (PCH6) is a rare mitochondrial disease resulting from mutations in the RARS2 gene. The typical presentation includes lactic acidosis, encephalopathy, seizures, nutritional problems, hypoglycemia and developmental delay.
Case study: Here we describe a two-month-old girl that was transferred to our ICU with suspected metabolic disease. After birth she presented with respiratory distress and feeding difficulties. Work up revealed lactic acidosis, hypoglycemia, elevated aminotransferase. CBC was normal and infection was ruled out. An MRI was completed showing cerebral, cerebellar and vermis atrophy.
She was re-admitted after a month with feeding difficulties. Work up revealed again lactic acidosis, hypoglycemia, and elevated aminotransferase, but now a hemoglobin of 5.4 mg/dl and elevated ferritin were seen. Treatment was initiated including RBC. She returned ten days after due to fever, vomiting and diarrhea. Liver enzymes and ferritin were again elevated and hemoglobin decreased to 7mg/dl.
Fasting was initiated on arrival to our institution because of recurrent diarrhea and resolved after switching to amino acid-based formula. A normal critical sample was obtained at hypoglycemia, which resolved after nutritional intervention including frequent eating and supplement of baby-calorie. Exome testing including mitochondrial genome identified compound heterozygosity for RARS2 gene: c.1A>G, p(Met1?) classified as pathogenic/likely pathogenic and was previously reported as related to PCH6, and c.1588C>T, classified as a variant of uncertain significance, a rare variant predicted to be pathogenic.
Conclusion: The clinical presentation including lactic acidosis, elevated aminotransferase, nutritional problems, hypoglycemia and brain MRI findings are consistent with previous descriptions of PCH6. This patient presented also with anemia as part of her metabolic crisis episodes, which might be an expanding spectrum of RARS2 phenotype.
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