Evidence for Mitochondrial Dysfunction in Prader-Willi Syndrome

Jūs esate čia

Rekomenduojame aplankyti

Laboratorinė medicina. 2015,
t. 17,
Nr. 1,
p. 37 -
42

Summary

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder due to loss of expression of paternally expressed genes from an imprinted region 15q11.2-q13. Loss of expression of SNORD116 gene cluster was recently described as a cause.

PWS is characterised by a variety of different symptoms progressing through the characteristic phases: muscul ar hypotonia leading to feeding difficulties, failure to thrive and other problems in neonatal/infantile period, delayed motor development, hyperphagia and characteristic nutrition-associated behaviours leading to morbid obesity, multiple endocrine disturbances, characteristic dysmorphic features, orthopaedic and other associated problems.

Several lines of evidence including clinical features, histological, biochemical and gene expression analyses in both PWS patients and animal models point to possible mitochondrial dysfunction in PWS. Muscular hypotonia, reduced muscle mass and decreased energy expenditure are constant features of PWS. Decreased plasma CoQ10 levels, increased carnitine ester to carnitine ratios, histological changes in PWS patient and animal model muscle specimen and differential expression of mitochondria-associated genes all point to possible mitochondrial dysfunction.

More extensive studies in obesity, type 2 diabetes and sarcopenia of aging show mitochondrial biogenesis and fusion/ fission mechanism derangements through PGC-1a and STK11-AMPK-SIRT1-PPARGC 1-a pathway as a possible pathogenetic mechanism of mitochondrial dysfunction in these complex common diseases. Mitochondriogenesis-eni hancing treatment methods were recently described.

Several lines of evidence point to mitochondrial dysfunction in PWS; more extensive investigations performed in obesity and other conditions associated with mitochondrial dysfunction could provide hints for further directions of investigations in PWS.

© 2024, Lietuvos laboratorinės medicinos draugija