Electron Microscopy Can Still Have a Role in the Diagnosis of Selected Inborn Errors of Metabolism

Abstract

Many anatomic pathology laboratories no longer have electron microscopy facilities. A retrospective review of autopsies was performed to identify cases of inborn errors of metabolism (IEM) and determine the contribution of electron microscopy in making the diagnosis in those cases. Over a period of 17 years, there were 900 perinatal and pediatric autopsies. There were 7 cases (1%) of IEM, including 4 cases of Pompe disease, 1 case of I-cell disease, 1 case of bile acid synthesis defect, and 1 case of mitochondrial disease (Leigh syndrome). Electron microscopy was important in the diagnosis of I-cell disease and Pompe disease in our series. This technique enabled a prenatal diagnosis to be made from a chorionic villus biopsy in 2 cases with a positive family history. In less developed countries where upfront genetic testing may be too expensive and may need international referral, electron microscopy can still be useful for diagnosis of IEM, providing an affordable alternative with a more rapid turnaround time compared to gene mutation analysis or enzyme assay. Results can be used both for patient management and as a screen for which cases might benefit from genetic testing.