Original article
Cardiac Manifestations in Oxidative Phosphorylation Disorders of Childhood

https://doi.org/10.1016/j.jpeds.2006.12.047Get rights and content

Objective

To determine the frequency, type, and severity of cardiac involvement in pediatric patients with oxidative phosphorylation (OXPHOS) disorders.

Study design

Retrospective review of clinical and laboratory records of all patients with definitive OXPHOS disorders diagnosed and treated at the Royal Children’s Hospital in Melbourne between 1984 and 2005.

Results

Of a total of 89 patients (male:female ratio 1.5:1) 29 (33%) had cardiac involvement: 9 as presenting symptoms, 9 developing on follow-up, and 11 with subclinical cardiac findings. Leigh or Leigh-like syndrome and complex I and combined complex I, III, and IV deficiencies were the most common clinical and laboratory diagnoses, respectively. Clinically symptomatic patients had hypertrophic cardiomyopathy (5 patients), dilated cardiomyopathy (4 patients), combined ventricular hypertrophy and systolic dysfunction (3 patients), and left ventricular noncompaction (3 patients) at first assessment. A change in the type of cardiomyopathy was noted on follow-up in 2 patients. Conduction and rhythm abnormalities were present in 7 symptomatic patients.

Conclusions

Cardiac assessment in children with OXPHOS disorders may reveal subclinical abnormalities of cardiac function. Patients who present with primary cardiac features have a poor prognosis. OXPHOS disorders should be considered in the differential diagnosis of children presenting with otherwise unexplained cardiomyopathy.

Section snippets

Methods

We conducted a retrospective review of clinical and laboratory records of all patients with definitive OXPHOS disorders diagnosed between 1984 and 2005 in the Mitochondrial Research Laboratory at the Murdoch Children Research Institute and treated at the Royal Children’s Hospital, Melbourne. The material used included biopsies taken for the investigation of a possible metabolic disease, explanted hearts at transplantation, and material collected at autopsy. The diagnosis of an OXPHOS disorder

Results

The clinical, enzymatic, and molecular findings of the whole cohort of patients are detailed in Table I. There were 89 patients, including 54 males and 35 females (male:female ratio 1.5:1). The median age at presentation of the 89 patients was 6 months (range: intrauterine to 15 years). The majority of patients had Leigh- or Leigh-like disease (27/89) and mitochondrial cytopathy (25/89), defined as a multisystemic disorder (affecting the muscular system2, central nervous system2, visual and

Discussion

Cardiac involvement in patients with OXPHOS defects has been reported in several series, with varying prevalence, type, and severity. There is some difficulty in comparing the results of the cited studies2, 3, 7, 8, 11, 12 because of the different diagnostic criteria used and possible ascertainment biases as a result of different inclusion criteria. Hence, the true prevalence of cardiac involvement in OXPHOS disorders is unclear. We believe that our systematic review of the clinical, enzymatic,

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    Supported by grants and a Senior Research Fellowship (DRT) from the National Health and Medical Research Council (NHMRC) of Australia.

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