Minimum birth prevalence of mitochondrial respiratory chain disorders in children

Mitochondrial respiratory chain disorders comprise a group of perhaps several hundred different genetic diseases. Each individual disorder is rare, but collectively they account for substantial use of health care resources. However, few accurate data on prevalence are available due to problems such as variation in clinical presentation, age of onset, referral practices and limitations of diagnostic methodologies. With this retrospective study, we aimed to determine the minimum birth prevalence of respiratory chain disorders that have onset in childhood, that is the proportion of births that will have onset of symptoms caused by a respiratory chain defect by 16 years of age. Of the 1 706 694 children born in the three south-eastern states of Australia (New South Wales, Victoria and South Australia) between January 1st 1987 and December 31st 1996, samples from 430 were referred for investigation of a respiratory chain disorder. Definite diagnosis of a respiratory chain disorder was made in 86 cases based on defined clinical, pathological, enzyme and molecular criteria. Age at presentation ranged from 0 to 129 months (median 4 months). The total data set predicts a minimum birth prevalence for respiratory chain disorders in children of 5.0/100 000 [95% confidence interval (CI) 4.0-6.2]. A significantly higher figure of 58.6/100 000 (95% CI 34.7-92.6) was noted for Australian families of Lebanese origin. Clinical awareness of respiratory chain disorders and investigation methods have improved since 1987, but not all affected children would have been recognized as such from the more recent years. The minimum birth prevalence of 6.2/100 000 (95% CI 4.5-8.4) for the 43 patients born between 1991 and 1994 is thought to be a more accurate estimate for respiratory chain disorders presenting in childhood. Combining our data with a previous study on prevalence of adult-onset respiratory chain disorders predicts a minimum birth prevalence of 13.1/100 000 or 1/7634 for respiratory chain disorders with onset at any age.