Inherited paediatric neurometabolic disorders,can brain magnetic resonance imaging predict?

Objectives:To evaluate diagnostic capability of brain magnetic resonance imaging (MRI) in detection of inherited neurometabolic disorders.Methods:This retrospective observational study was performed in Radiology Department at our Hospital in Dhahran, from January 2013 to January 2020. We evaluated brain MRIs of children (under 5) who were referred to pediatric neurology for clinical suspicion of neuro-developmental delay and metabolic disease. Known perinatal ischemia and birth trauma cases were excluded. Imaging criteria included: (i) bilateral symmetric white matter signal abnormality, (ii) diffusion restriction affecting bilateral deep grey nuclei with or without brainstem involvement, (iii) brain atrophy or edema with abnormal white matter signal, (iv) characteristic MR spectroscopic finding. Presence of any one of these findings was considered positive for neurometabolic disease. Two neuroradiologists interpreted MRIs with substantial interobserver agreement. Diagnoses were confirmed on biochemical/ metabolic screening and genetic testing. A 2 × 2 contingency table was used for results. Chi square test was used to determine association.Results:Out of 133 cases, 72 (49 males, 90% AR) were found to have neurometabolic disorders. Sensitivity, specificity, positive and negative predictive values were calculated as 81.94% (CI, 71.11-90.02), 67.21% (CI, 54.00-78.69), 74.68% (CI, 66.96-81.11) and 75.93% (CI, 65.16-84.17) respectively. Findings were found significant (p-value=0.0001).Conclusion:Brain MRI can help to predict inherited neurometabolic disorders considering certain findings.

Metabolic diseases can be either inherited (inborn errors of metabolism) or acquired. Inborn errors of metabolism (IEMs) that primarily affect the central nervous system are referred to as neurometabolic diseases, and usually occur in neonates and infants.1 These diseases involve genetic defects that result in certain enzyme deficiency leading to deficiency of essential metabolite or toxic accumulation of others with specific biochemical and molecular abnormalities. Clinical presentations may be confusing and potentially lead to delay in diagnosis and treatment.2 Overall incidence of this group of disorders may vary from region to region, being much higher in communities with consanguineous marriages, ranging from 1.2 to 2 per 100,000 live births.3 Most exhibit autosomal recessive (AR) mode of inheritance. Neurometabolic disorders can be classified by various methods based on clinical and biochemical characteristics, area of brain involvement, or cellular organelle.4 Imaging based classification includes leukodystrophy (primary involvement of white matter due to genetic abnormality), leukoencephalopathy (secondary involvement of white matter either due to genetic or acquired systemic disorder), poliodystrophy (predominant involvement of grey matter), and pandydystrophy (mixed involvement of both white and grey matter).5 Central nervous system white matter is usually affected,6 and can result from various pathologic process like delayed myelination (myelin maturation delayed for expected age), hypomyelination (scarcity of myelin or arrest in myelination process), dysmyelination (deposition of abnormally composed fragile myelin), demyelination (secondary loss of myelin that may have been previously normal) and myelinopathy (vacuolating due to deranged brain iron and water hemostasis).Magnetic resonance imaging is the modality of choice for evaluation of neurometabolic disorders.7 Analyzing pattern recognition in MR imaging and clinical clues help to narrow the differential, tailor subsequent laboratory (targeted metabolomics) or genetic investigations (either requiring single gene testing or broad-spectrum genetic testing i.e., whole exome sequencing/ WES).4 The MRI can be helpful in diagnostic workup of various diseases and may be decisive for early management even before arrival of costly and time-consuming biochemical or genetic testing results.8 We therefore sought to highlight ability of MRI in predicting diagnoses of inherited neurometabolic disorders in neonates and young children considering certain MRI findings.