Cerebral Ultrasonography of Cytotoxic Edema in a Newborn With a Mitochondrial Disorder

A preterm infant born at 34 weeks’ gestation weighing 1500 g due to intrauterine growth restriction (IUGR) presented with persistent hyperlacticaemia. Clinical evolution was favorable in the first weeks, and the early cerebral ultrasound (cUS) did not show abnormalities. On a routine blood test at age 6 days, severe hyperlacticaemia (63 mg/dL [to convert to millimoles per liter, multiply by 0.111]) was detected. Findings of physical and neurological examination were unremarkable, and hyperlacticaemia was initially attributed to a transient disorder common in newborns with IUGR. Nevertheless, moderate hyperlacticaemia (27 to 36 mg/dL) without acidosis persisted. Sepsis, heart failure, and pharmacological causes were ruled out, and a metabolic workup was conducted. Urine analysis showed unspecific high levels of Krebs cycle metabolites, reported as possibly transient, and plasmatic amino acids showed a mild alanine elevation. A second cUS performed at age 19 days showed symmetrical increased echogenicity of the subthalamic nuclei. Magnetic resonance imaging (MRI; MR 3 Tesla; Philips Ingenia) was subsequently performed, which showed mild restriction of the subthalamic nuclei and colliculi in diffusion-weighted images with normal T1-weighted and T2-weighted images (Figure 1). Considering analytical and radiological abnormalities, a mitochondrial disease was suspected, and appropriate cofactors were initiated. Follow-up cUS confirmed persistent increased echogenicity of the subthalamic nuclei, colliculi, and globi pallidi. A second MRI was performed at 42 days, showing at this moment clear abnormal signal intensity of these areas on T1-weighted and T2-weighted images (Figure 2) as well as a more obvious restriction diffusion, indicating cytotoxic edema without lactate peak in the magnetic resonance spectroscopy. Genetic study confirmed a mitochondrial transfer RNA translation optimization 1 (MTO1) deficiency. This disease typically displays hypertrophic cardiomyopathy, lactic acidosis, development delay, and high early mortality rates for those with neonatal presentation.¹ This patient died at age 8 months following a metabolic decompensation with severe lactic acidosis. Up to then, he showed progression of lactic acidosis and only mild abnormalities in eye gaze and muscle tone.