Neurodevelopmental manifestations of mitochondrial disease

Abstract

Mitochondrial disease is an increasingly recognized but widely heterogeneous group of multisystemic disorders that commonly involve severe neurodevelopmental manifestations in childhood. This review explores the presentation, genetic basis, and diagnostic evaluation of primary mitochondrial disease. Emphasis is placed on neurodevelopmental findings that may be encountered by a Developmental Pediatrician that should provoke consideration of a mitochondrial disorder. The inheritance patterns and mechanisms by which mutations in genes located in either the nuclear or mitochondrial genomes can cause mitochondrial diseases are discussed. A general overview of the current diagnostic evaluation that can be readily initiated by the Developmental Pediatrician is provided, along with a summary of currently available treatment options.

FIGURE 1. Initiating the diagnostic evaluation for suspected mitochondrial disease

The Developmental Pediatrician can initiate a multi-faceted clinical and baseline laboratory evaluation to screen for multi-systemic involvement, including intermediary metabolic findings, which may support the diagnosis of mitochondrial disease. Abnormalities on these screening studies should prompt referral to a Metabolic disease specialist for further consideration of specific genetic and/or tissue studies (see text). *, since metabolic abnormalities may be seen only intermittently at the time of stress in mitochondrial disease, indicated blood and urine studies may need to be performed at baseline and then repeated at time of illness (i.e., fever or dehydration).