Mitochondrial complex III deficiency with ketoacidosis and hyperglycemia mimicking neonatal diabetes

Abstract

Hyperglycemia is a rare presenting symptom of mitochondrial disorders. We report a case of a young girl who presented shortly after birth with ketoacidosis, hyperlactatemia, hyperammonemia, and insulin-responsive hyperglycemia. Initial metabolic work-up suggested mitochondrial dysfunction. Given our patient’s unusual presentation, whole-exome sequencing (WES) was performed on the parent–offspring trio. The patient was homozygous for the c.643C>T (p.Leu215Phe) variant in CYC1, a nuclear gene which encodes cytochrome c1, a subunit of respiratory chain complex III. Variants in this gene have only been previously reported in two patients with similar presentation, one of whom carries the same variant as our patient who is also of Sri Lankan origin. Primary complex III deficiencies are rare and its phenotypes can vary significantly, even among patients with the same genotype.