Preliminary observations of mitochondrial dysfunction in Prader–Willi syndrome

• Published in: American journal of medical genetics. Part A Vol. 176; no. 12; pp. 2587 - 2594
• Main Authors: Butler, Merlin G., Hossain, Waheeda A., Tessman, Robert, Krishnamurthy, Partha C.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2018; Wiley Subscription Services, Inc
• Subjects: Adenosine Triphosphate - metabolism; Adolescent; Adult; ATP; Bioenergetics; Case-Control Studies; Cell lines; Cell Respiration; Child; Child, Preschool; Children; Chromosomes, Human, Pair 15; Electron transport; Energy expenditure; Female; fibroblasts; Genomic imprinting; healthy controls; Humans; Hyperphagia; Infant; Male; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; mitochondrial assays and dysfunction; Phenotype; Physical activity; Prader-Willi syndrome; Prader-Willi Syndrome - diagnosis; Prader-Willi Syndrome - genetics; Prader-Willi Syndrome - metabolism; Respiration; Suckling behavior; Young Adult; fibroblasts; Prader-Willi syndrome; mitochondrial assays and dysfunction; healthy controls
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.40526

Prader–Willi syndrome (PWS) is a complex multisystem disorder because of errors in genomic imprinting with severe hypotonia, decreased muscle mass, poor suckling, feeding problems and failure to thrive during infancy, growth and other hormone deficiency, childhood‐onset hyperphagia, and subsequent obesity. Decreased energy expenditure in PWS is thought to contribute to reduced muscle mass and physical activity but may also relate to cellular metabolism and disturbances in mitochondrial function. We established fibroblast cell lines from six children and adults with PWS and six healthy controls for mitochondrial assays. We used Agilent Seahorse XF extracellular flux technology to determine real‐time measurements of several metabolic parameters including cellular substrate utilization, Adenosine Triphosphate (ATP)‐linked respiration, and mitochondrial capacity in living cells. Decreased mitochondrial function was observed in the PWS patients compared to the healthy controls with significant differences in basal respiration, maximal respiratory capacity, and ATP‐linked respiration. These results suggest disturbed mitochondrial bioenergetics in PWS although the low number of studied subjects will require a larger subject population before a general consensus can be reached to identify if mitochondrial dysfunction is a contributing factor in PWS.