Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)
Presentation
Uneventful neonatal period. Presented with fever, vomiting and seizure. Intubated in view of metabolic acidosis HCO3 6.1.
Patient Data
CASE OF THE MONTH: This case was selected as the Case of the Month for May 2023.
Bilateral basal ganglia calcifications. Patchy ill-defined cortical hypodensities involving bilateral occipital lobes with associated cerebral sulci effacement.
Cortical thickening of bilateral occipital lobes with predominant involvement at a parasagittal location, slightly more on the left, associated with T1 hypointense, T2 / FLAIR hyperintense signal, and minimal adjacent subcortical involvement. These aforementioned areas have high DWI signals but only small foci have low ADC signals, which are suggestive of acute infarcts. There are also foci of high DWI signals scattered at bilateral cerebellar hemispheres and right globus pallidus; some with corresponding low ADC signals. Susceptibility artifact at basal ganglia is in keeping with the calcifications noted in CT.
No grey matter heterotopia. Anterior and posterior cerebral circulations are normal. No aneurysm or arteriovenous malformation.
Sampling on MR spectroscopy demonstrates elevated lactate peak in otherwise normal-appearing brain parenchyma.
Summary:
Overall findings could represent mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Suggest clinical correlation (eg: family history / maternal inheritance, CSF results / molecular genetic testing). Less likely differentials: other mitochondrial disorders.
Case Discussion
Inborn Error Metabolism (IEM) Screening, Blood Spot Test Report: Normal profile
PTH (1-84): 3.8 pmol/L (Normal range 1.6 - 6.0)
The pediatrician proceeded with a lumbar puncture. The lactate level for the CSF sample was 9.28 mmol/L (normal reference range 0.50 - 2.20). Culture and Sensitivity of CSF: No growth.
PCR and Direct Sequencing of MT-TL1 tRNA gene
DNA change: m.3243A>G
Approximately 70% heteroplasmy
Classification: Pathogenic
Interpretation/Comment:
The MT-TL1: m.3243A>G mutation was detected at approximately 70% of heteroplasmy in his blood-derived DNA sample.
The mutation is maternally inherited, therefore there is NO risk of transmitting the mutation to any children he may have in future.
Testing should be offered to appropriate maternal relatives as they are at risk of inheriting the MT-TL1: m.3243A>G mutation and developing associated symptoms.
Recommend referral to Clinical Geneticist