Elsevier

Pediatric Neurology

Volume 38, Issue 6, June 2008, Pages 395-397
Pediatric Neurology

Original article
Ophthalmologic Presentation of Oxidative Phosphorylation Diseases of Childhood

https://doi.org/10.1016/j.pediatrneurol.2008.02.003Get rights and content

To investigate ophthalmologic manifestations in children with definitive oxidative phosphorylation disorders, a retrospective review was conducted of clinical and laboratory records of all such pediatric patients (n = 103) diagnosed and treated at one center between 1983 and 2006. All were residents of Victoria, Australia. Nystagmus or roving eye movements were the most common ophthalmologic manifestations as a presenting symptom of disease (13/20) and were the sole manifestation at presentation in 10/13 patients. Divergent strabismus was a presenting symptom in 5/20 patients and was the sole manifestation at presentation in 3/20 patients. Abnormal eye movements were noted in 6 patients and strabismus was noted in 4 patients with Leigh's or Leigh-like disease; in 9 of these 10 patients, Leigh's disease was the result of complex I deficiency. Altogether, ophthalmologic manifestations were noted at presentation in 12/35 patients with complex I deficiency. External ophthalmoplegia in conjunction with ptosis was the presenting symptom in 3/20 patients, all with Kearns-Sayers syndrome. Patients suspected of having oxidative phosphorylation disorders should be referred for ophthalmologic examination. Prospective studies are needed for a comprehensive elucidation of the ophthalmologic findings in these disorders.

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

References (12)

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