RT Journal Article
SR Electronic
T1 Neonatal-onset mitochondrial disease: clinical features, molecular diagnosis and prognosis
JF Archives of Disease in Childhood - Fetal and Neonatal Edition
JO Arch Dis Child Fetal Neonatal Ed
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP fetalneonatal-2021-321633
DO 10.1136/archdischild-2021-321633
A1 Tomohiro Ebihara
A1 Taro Nagatomo
A1 Yohei Sugiyama
A1 Tomoko Tsuruoka
A1 Yoshiteru Osone
A1 Masaru Shimura
A1 Makiko Tajika
A1 Tetsuro Matsuhashi
A1 Keiko Ichimoto
A1 Ayako Matsunaga
A1 Nana Akiyama
A1 Minako Ogawa-Tominaga
A1 Yukiko Yatsuka
A1 Kazuhiro R Nitta
A1 Yoshihito Kishita
A1 Takuya Fushimi
A1 Atsuko Imai-Okazaki
A1 Akira Ohtake
A1 Yasushi Okazaki
A1 Kei Murayama
YR 2021
UL http://fn.bmj.com/content/early/2021/09/28/archdischild-2021-321633.abstract
AB Objective Neonatal-onset mitochondrial disease has not been fully characterised owing to its heterogeneity. We analysed neonatal-onset mitochondrial disease in Japan to clarify its clinical features, molecular diagnosis and prognosis.Design Retrospective observational study from January 2004 to March 2020.Setting Population based.Patients Patients (281) with neonatal-onset mitochondrial disease diagnosed by biochemical and genetic approaches.Interventions None.Main outcome measures Disease types, initial symptoms, biochemical findings, molecular diagnosis and prognosis.Results Of the 281 patients, multisystem mitochondrial disease was found in 194, Leigh syndrome in 26, cardiomyopathy in 38 and hepatopathy in 23 patients. Of the 321 initial symptoms, 236 occurred within 2 days of birth. Using biochemical approaches, 182 patients were diagnosed by mitochondrial respiratory chain enzyme activity rate and 89 by oxygen consumption rate. The remaining 10 patients were diagnosed using a genetic approach. Genetic analysis revealed 69 patients had nuclear DNA variants in 36 genes, 11 of 15 patients had mitochondrial DNA variants in five genes and four patients had single large deletion. The Cox proportional hazards regression analysis showed the effects of Leigh syndrome (HR=0.15, 95% CI 0.04 to 0.63, p=0.010) and molecular diagnosis (HR=1.87, 95% CI 1.18 to 2.96, p=0.008) on survival.Conclusions Neonatal-onset mitochondrial disease has a heterogenous aetiology. The number of diagnoses can be increased, and clarity regarding prognosis can be achieved by comprehensive biochemical and molecular analyses using appropriate tissue samples.Data are available on reasonable request. Deidentified participant data are available from corresponding author, Kei Murayama. kmuraya@mri.biglobe.ne.jp. ORCID iD 0000-0002-3923-8636. Data are available on reasonable request.