Neurodevelopmental Manifestations of Mitochondrial Disease

Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA, USA. .
Journal of developmental and behavioral pediatrics: JDBP (Impact Factor: 2.13). 09/2010; 31(7):610-21. DOI: 10.1097/DBP.0b013e3181ef42c1
Source: PubMed


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.

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    ABSTRACT: Mitochondrial disease is a heterogeneous group of energy metabolism disorders that present across all ages with a wide range of ocular or multisystemic manifestations. This review focuses on recent progress made toward understanding the various ophthalmologic manifestations of primary mitochondrial diseases and discusses the implications of mitochondrial dysfunction, placing particular emphasis on recent investigations into the pathogenesis and emerging therapies for mitochondrial-based ophthalmologic disorders. Novel pathogenic mitochondrial DNA mutations continue to be detected in diverse ethnic populations for primary mitochondrial ophthalmologic disorders that commonly affect the optic nerve, retina, and extraocular muscles. Promising antioxidant and gene therapy approaches are being actively investigated to treat these ophthalmologic manifestations, as in Leber's hereditary optic neuropathy. Mitochondrial dysfunction is also increasingly implicated in common ophthalmologic disorders of aging, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Several proteins recently recognized to play a role in the mitochondrial oxidative stress response within retinal cells, such as prohibitin and MMP2, may serve as novel biomarkers and therapeutic targets for common ophthalmologic disorders. Therapies that inhibit mitochondrial function and induce apoptosis within tumor cells, such as EDL-155 and curcumin, may offer novel therapeutic agents for ocular neoplasms such as retinoblastoma and uveal melanoma. Primary mitochondrial genetic disease manifestations can involve almost all aspects of the eye. Mitochondrial dysfunction is increasingly recognized as playing a causative role in the common ophthalmologic disorders in aging. This understanding has unleashed a range of emerging therapeutic approaches for mitochondrial-based ophthalmologic disorders directed at optimizing mitochondrial function.
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