Objective To delineate the clinical and genetic characteristics of a girl featuring motor retardation, language retardation and regression, and light persisting diarrhea. Methods The patient was clinically examined and tested by tandem mass spectrometry and next generation sequencing. Results The proband could not stand and walk alone, and had light persisting diarrhea. She manifested language development retardation and regression. Laboratory tests were all normal, but the screening of metabolic disorders for urine and blood showed deficiency of short chain coenzyme A dehydrogenase due to elevated ethylmalonic acid and butyryl carnitine. By next generation sequencing, two compound heterozygous mutations of the ETHEl gene, c. 2T〉A and c. 488G〉A, were discovered in the proband, which were respectively inherited from her father and mother. Bioinformatics analysis predicted both mutations to be pathogenic. The patient was diagnosed with ethylmalonic encephalopathy. Vitamin B1 , B2 , Coenzyme Q10, and L-carnitine were prescribed. The patient deteriorated and required liver transplantation at 4-year-l- month. Conclusion Based on the clinical and genetic analysis, the proband was diagnosed with ethylmalonic encephalopathy caused by ETHEl gene mutation. Next generation sequencing has provided a powerful tool for the diagnosis of such disorders.
Chinese Journal of Medical Genetics