The clinical spectrum of mitochondrial diseases in neonates and young children and approach to diagnosis

Abstract

Mitochondrial diseases are becoming more frequently diagnosed in neonates and small children. Different clinical presentations are possible and specific investigations need to be performed in order to get to the right molecular diagnosis necessary for further genetic counseling. MtDNA or nuclear genes can be investigated after biochemical work-up in the affected tissue. In the neonate, severe presentation may lead to early death, so taking the possible mitochondrial disease in consideration is essential, especially in case of severe lactic acidosis, encephalopathy, myopathy, cardiomyopathy or hepatopathy. In infancy, there are three syndromes that can occur more frequently: Pearson’s syndrome due to deletion of mitochondrial DNA; Leigh’s encephalopathy, a progressive neurodegenerative disorder with many different mitochondrial gene mutations; and Alpers’ disease, progressive gray matter degeneration due to mutations in the POLG gene. Different organ involvement is seen in mtDNA depletion syndromes and finally one should also consider CoQ10 deficiency in certain clinical presentations.