Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency.
Olivier FortinKelsey ChristoffelAbdullah ShoaibCharu VenkatesanKate CilliJason W SchroederCesar AlvesRebecca D GanetzkyJamie L FraserPublished in: medRxiv : the preprint server for health sciences (2024)
Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including PDHA1 . Typical neonatal brain imaging findings in PDCD have been described, with a focus on malformative features and chronic encephaloclastic changes. However, fetal brain MRI imaging in confirmed PDCD has not been comprehensively described. We sought to demonstrate the prenatal neurological and systemic manifestations of PDCD determined by comprehensive fetal imaging and genomic sequencing. All fetuses with a diagnosis of genetic PDCD who had undergone fetal MRI were included in the study. Medical records, imaging data, and genetic testing results were reviewed and reported descriptively. Ten patients with diagnosis of PDCD were included. Most patients had corpus callosum dysgenesis, abnormal gyration pattern, reduced brain volumes, and periventricular cystic lesions. One patient had associated intraventricular hemorrhages. One patient had a midbrain malformation with aqueductal stenosis and severe hydrocephalus. Fetuses imaged in the second trimester were found to have enlargement of the ganglionic eminences with cystic cavitations, while those imaged in the third trimester had germinolytic cysts. Fetuses with PDCD have similar brain MRI findings to neonates described in the literature, although some of these findings may be subtle early in pregnancy. Additional features, such as cystic cavitations of the ganglionic eminences, are noted in the second trimester in fetuses with PDCD, and these may represent a novel early diagnostic marker for PDCD. Using fetal MRI to identify these radiological hallmarks to inform prenatal diagnosis of PDCD may guide genetic counseling, pregnancy decision-making, and neonatal care planning.
Keyphrases
- gestational age
- resting state
- contrast enhanced
- high resolution
- magnetic resonance imaging
- preterm birth
- white matter
- healthcare
- functional connectivity
- diffusion weighted imaging
- cerebral ischemia
- genome wide
- copy number
- palliative care
- pregnancy outcomes
- systematic review
- end stage renal disease
- pregnant women
- case report
- computed tomography
- decision making
- ejection fraction
- magnetic resonance
- newly diagnosed
- single cell
- dna methylation
- machine learning
- chronic kidney disease
- prognostic factors
- blood brain barrier
- early onset
- cerebrospinal fluid
- quality improvement
- big data
- mass spectrometry
- electronic health record
- transcription factor
- fluorescence imaging
- hiv infected