Original articleOphthalmologic Presentation of Oxidative Phosphorylation Diseases of Childhood
Introduction
Mitochondria generate energy for cellular function through the oxidative phosphorylation system, which includes the mitochondrial respiratory chain comprising complexes I to IV and ATPase (complex V). Disorders of the mitochondrial oxidative phosphorylation system may occur in any organ and at any age, and can be classified according to clinical, biochemical, or molecular criteria. The clinical criteria are diverse, and signs and symptoms may relate to one or, more commonly, several systems. The biochemical criteria are based on demonstrated defects in the mitochondrial respiratory chain or in ATPase activity. The demonstration of causative mutations in either the nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) provides a molecular diagnosis.
Specific ophthalmologic diseases have been described in conjunction with some mitochondrial oxidative phosphorylation disorders. These usually include entities with typically later onset, such as Leber's hereditary optic neuropathy or chronic progressive external ophthalmoplegia [1]. In addition, ophthalmologic manifestations have been reported in patients with the syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) [2], myoclonus epilepsy with ragged red fibers (MERRF syndrome) [2], and Leigh's syndrome [3]. Progressive external ophthalmoplegia has been reported in patients with Kearns-Sayers syndrome [4], [5] and in patients harboring mutations in the polymerase gamma (POLG) gene [6].
The present study investigated ophthalmologic manifestations at presentation in a large cohort of pediatric patients with oxidative phosphorylation disorders.
Section snippets
Methods
The clinical and laboratory records of all patients, residents of Victoria, with definitive oxidative phosphorylation disorders diagnosed between 1983 and 2006 in the Mitochondrial Research Laboratory at the Murdoch Children Research Institute and treated at the Royal Children's Hospital, Melbourne, were reviewed. Patients referred from centers outside Victoria were excluded from this review. The diagnosis of an oxidative phosphorylation disorder was based on previously published diagnostic
Results
The review population was 103 patients. The diagnosis was based on one or more of the following: an oxidative phosphorylation enzyme complex defect (79 patients; 77%), pathologic enzyme histochemistry or electron microscopy of skeletal muscle biopsy (6 patients), and molecular diagnoses (53 patients; 51%).
Ophthalmologic manifestations were noted as the presenting symptom of oxidative phosphorylation disease in 20 patients (median age at presentation, 4 months; range, 0 to 168 months;
Discussion
The present investigation is novel in being a pediatric population-based study showing data on the frequency and type of ophthalmologic manifestations at time of presentation with oxidative phosphorylation disorders, in a large cohort of patients diagnosed at a single laboratory according to established criteria and treated at a single tertiary-referral pediatric medical center. Clinical, enzymatic, and molecular findings were combined with ophthalmologic findings at presentation to analyze
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Neurometabolic disease and the eye
2012, Pediatric Ophthalmology and Strabismus: Expert Consult - Online and PrintClinical manifestations in children with mitochondrial diseases
2010, Pediatric NeurologyCitation Excerpt :According to our observations, clinical central nervous system features in children with mitochondrial diseases also included altered levels of consciousness, respiratory disorders, external ocular motility limitation, and a situation mimicking sudden infant death syndrome. Clinical ophthalmologic manifestations of mitochondrial diseases were reported to account for at least 20% of patients [22], in whom abnormal eye movements and divergent strabismus were the most notable features. Our study indicated that 39.1% of patients with mitochondrial diseases exhibited variable ophthalmologic involvement.
Reply to 'the spectrum of neuro-ophthalmologic involvement in mitochondrial disorders is broad'
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