Mitochondrial diseases in North America: An analysis of the NAMDC Registry.
Creator
Barca Emanuele; Long Yuelin; Cooley Victoria; Schoenaker Robert; Emmanuele Valentina; DiMauro Salvatore; Cohen Bruce H; Karaa Amel; Vladutiu Georgirene D; Haas Richard; Van Hove Johan L K; Scaglia Fernando; Parikh Sumit; Bedoyan Jirair K; DeBrosse Susanne D; Gavrilova Ralitza H; Saneto Russell P; Enns Gregory M; Stacpoole Peter W; Ganesh Jaya; Larson Austin; Zolkipli-Cunningham Zarazuela; Falk Marni J; Goldstein Amy C; Tarnopolsky Mark; Gropman Andrea; Camp Kathryn; Krotoski Danuta; Engelstad Kristin; Rosales Xiomara Q; Kriger Joshua; Grier Johnston; Buchsbaum Richard; Thompson John L P; Hirano Michio
Publisher
Neurology. Genetics
Date
2020
2020-04
Description
Objective: To describe clinical, biochemical, and genetic features of participants with mitochondrial diseases (MtDs) enrolled in the North American Mitochondrial Disease Consortium (NAMDC) Registry. Methods: This cross-sectional, multicenter, retrospective database analysis evaluates the phenotypic and molecular characteristics of participants enrolled in the NAMDC Registry from September 2011 to December 2018. The NAMDC is a network of 17 centers with expertise in MtDs and includes both adult and pediatric specialists. Results: One thousand four hundred ten of 1,553 participants had sufficient clinical data for analysis. For this study, we included only participants with molecular genetic diagnoses (n = 666). Age at onset ranged from infancy to adulthood. The most common diagnosis was multisystemic disorder (113 participants), and only a minority of participants were diagnosed with a classical mitochondrial syndrome. The most frequent classical syndromes were Leigh syndrome (97 individuals) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (71 individuals). Pathogenic variants in the mitochondrial DNA were more frequently observed (414 participants) than pathogenic nuclear gene variants (252 participants). Pathogenic variants in 65 nuclear genes were identified, with POLG1 and PDHA1 being the most commonly affected. Pathogenic variants in 38 genes were reported only in single participants. Conclusions: The NAMDC Registry data confirm the high variability of clinical, biochemical, and genetic features of participants with MtDs. This study serves as an important resource for future enhancement of MtD research and clinical care by providing the first comprehensive description of participant with MtD in North America.
Diagnosis of 'possible' mitochondrial disease: an existential crisis.
Creator
Parikh Sumit; Karaa Amel; Goldstein Amy; Bertini Enrico Silvio; Chinnery Patrick F; Christodoulou John; Cohen Bruce H; Davis Ryan L; Falk Marni J; Fratter Carl; Horvath Rita; Koenig Mary Kay; Mancuso Michaelangelo; McCormack Shana; McCormick Elizabeth M; McFarland Robert; Nesbitt Victoria; Schiff Manuel; Steele Hannah; Stockler Silvia; Sue Carolyn; Tarnopolsky Mark; Thorburn David R; Vockley Jerry; Rahman Shamima
Publisher
Journal of medical genetics
Date
2019
2019-03
Description
Primary genetic mitochondrial diseases are often difficult to diagnose, and the term 'possible' mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. In instances when a genetic diagnosis cannot be confirmed, a diagnosis of 'possible' mitochondrial disease may result in harm to patients and their families, creating anxiety, delaying appropriate diagnosis and leading to inappropriate management or care. A categorisation of 'diagnosis uncertain', together with a specific description of the metabolic or genetic abnormalities identified, is preferred when a mitochondrial disease cannot be genetically confirmed.
Subject
clinical genetics; diagnosis; evidence based practice; metabolic disorders
Diagnosis of 'possible' mitochondrial disease: an existential crisis.
Creator
Parikh Sumit; Karaa Amel; Goldstein Amy; Bertini Enrico Silvio; Chinnery Patrick F; Christodoulou John; Cohen Bruce H; Davis Ryan L; Falk Marni J; Fratter Carl; Horvath Rita; Koenig Mary Kay; Mancuso Michaelangelo; McCormack Shana; McCormick Elizabeth M; McFarland Robert; Nesbitt Victoria; Schiff Manuel; Steele Hannah; Stockler Silvia; Sue Carolyn; Tarnopolsky Mark; Thorburn David R; Vockley Jerry; Rahman Shamima
Publisher
Journal of medical genetics
Date
2019
2019-03
Description
Primary genetic mitochondrial diseases are often difficult to diagnose, and the term 'possible' mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. In instances when a genetic diagnosis cannot be confirmed, a diagnosis of 'possible' mitochondrial disease may result in harm to patients and their families, creating anxiety, delaying appropriate diagnosis and leading to inappropriate management or care. A categorisation of 'diagnosis uncertain', together with a specific description of the metabolic or genetic abnormalities identified, is preferred when a mitochondrial disease cannot be genetically confirmed.
Subject
clinical genetics; diagnosis; evidence based practice; metabolic disorders