Minimum birth prevalence of mitochondrial respiratory chain disorders in children

Abstract

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.

Mitochondrial Disease in Childhood: Nuclear Encoded

“…Therefore, the organs most reliant on mitochondrial energy production will be the most symptomatic to such defects, and these include the central nervous system, skeletal muscle, heart, endocrine organs, and kidney [2]. Once considered rare, the prevalence of primary mitochondrial disease is approximately 1:5000 [3]. Though the phenotypes are highly variable, many of these conditions are severe and progressive, and remain without proven effective therapies.…”

Tissue- and cell-type–specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model

“…Our data show that cellular context actively modifies RC deficiency manifestation in MELAS and that autophagy is a significant component of neuronal MELAS pathogenesis. mitochondria | disease modeling M itochondrial DNA (mtDNA) mutations cause a mitochondrial respiratory chain (RC) disease in 1:5,000 individuals in Western populations (1), and 1:200 of newborns carries a potentially pathogenic mtDNA mutation (2). After the original description of the first mtDNA mutations (3,4), more than 200 disease-causing mtDNA point mutations have been reported to underlie mitochondrial disease (5).…”

Mitochondrial Genetics

“…Estimates, based on clinical observations, indicate that as many as 1 in 5000 people in the North East of England have manifested mitochondrial disease, 35 with similar figures reported in other parts of the world. [36][37][38] Identifying and diagnosing mitochondrial genetic disease: general principles Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive, multisystem, disorder. However, clinical diagnosis can be difficult if patients do not present with 'classical mitochondrial' disease (see later).…”