Purpose or Case Report: Primary mitochondrial disorders (PMD) in newborns can be misdiagnosed as hypoxic-ischemic encephalopathy (HIE), clinically and radiologically. The purpose of this study is to describe the frequency and patterns of brain MRI findings in children with PMD diagnosed during the neonatal period.
Methods & Materials: In this retrospective IRB approved study, the MRI database was queried for subjects with PMD from 2000 to 2018. Patients with the genetic diagnosis of PMD before 30 days of life and available brain MRI were included. DNA etiology distribution (mitochondrial or nuclear), specific gene mutation, and patterns of MRI findings were described.
Results: Fourteen (11.8%) patients were included with a median age at MRI of 56 days (IQR 9-518) (8 males). Thirteen (93%) subjects had nuclear gene etiology, including three FBXL4, two TRMU, one SLC25A46, one SLC25A3, one FARS2, one LPIN1, two MRPL3, and two RRM2B. The only one newborn with mitochondrial etiology was a single large-scale deletion, clinically classifiable as Pearson syndrome. Two cases were diagnosed as Leigh Syndrome, the remaining 11(78.6%) were not phenotypically classifiable. Seven subjects (50%) died (median 101 days;IQR 52-183). Ten newborns had MR spectroscopy, all showing an abnormal lactate peak and in four cases this was the only MRI finding. The most common location of lesions was the deep white matter (n=6,42.9%). White matter cavitation was noted in two subjects, both with periventricular distribution and associated with hemorrhagic component. Hemorrhagic foci were also noted with periventricular distribution in another patient. Another common finding was involvement of the cerebellar dentate nuclei in 5 (35.7%), and ventriculomegaly in 4 subjects (28.6%). Basal ganglia and brainstem lesions were noted in 2 (14.3%) and 3 cases (21,4%), respectively. One subject, FARS2 mutation, had imaging findings consistent with stroke-like lesions compromising both occipitoparietal lobes, and the splenium of the corpus callosum, mimicking/overlapping findings of neonatal hypoglycemia.
Conclusions: Disease onset of PMD is not uncommon in newborns. Of note, these subjects have demonstrated a high frequency of nuclear gene mutation, rather than mitochondrial DNA. Lactate peak on spectroscopy can be the only imaging abnormality. White matter lesion was the most frequent finding, commonly associated with hemorrhage and cavitation. Basal ganglia and brainstem involvement, commonly observed in other PMD age groups and HIE patients, were uncommon.