Abstract
BackgroundBarth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5). The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients.MethodsPlasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs) and 14 healthy control males (8 - 21 yrs) was analyzed for two growth factors: IGF-1 (bound and free) and Growth Hormone (GH); and two inflammatory cytokines IL-6 and TNF-α using high-sensitivity enzyme-linked immunosorbent assays.ResultsThe average IL-6 and IL6:IGF ratio levels were significantly higher in the BTHS (p = 0.046 and 0.02 respectively). As for GH, there was a significant group by age interaction (p = 0.01), such that GH was lower for BTHS patients under the age of 14.4 years and higher than controls after age 14.4 years. TNF-α levels were not significantly different, however, the TNF-α:GH was lower in BTHS patients than controls (p = 0.01).ConclusionsComparison of two anabolic growth mediators, IGF and GH, and two catabolic cytokines, IL-6 and TNF-α, in BTHS patients and healthy age-matched controls demonstrated a potential imbalance in inflammatory cytokines and anabolic growth factors. Higher rates of IL-6 (all ages) and lower GH levels were observed in BTHS patients (under age 14.5) compared to controls. These findings may implicate inflammatory processes in the catabolic nature of Barth Syndrome pathology as well as provide a link to mitochondrial function. Furthermore, interactions between growth factors, testosterone and inflammatory mediators may explain some of the variability in cardiac and skeletal myopathies seen in Barth Syndrome.
Highlights
Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, called G4.5)
Growth anomalies have been widely reported in BTHS, there is a paucity of research on the contribution of catabolic/anabolic processes, the influence of inflammation and the potential link to alterations in growth factor levels in BTHS patients
We hypothesized that patients diagnosed with BTHS would have an imbalance in catabolic and anabolic mediators such that BTHS would have lower levels of growth factors and higher levels of inflammatory mediators compared to age-matched healthy controls. This study addresses this question by statistical analysis of Insulin-like growth factor (IGF)-1, Growth Hormone (GH), IL-6 and TNF-α plasma levels obtained from BTHS patients and healthy controls
Summary
Growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients. Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, called G4.5) This multi-system disorder is primarily characterized by the following pathologies: cardiomyopathy (dilated or hypertrophic), neutropenia (chronic, cyclic, or intermittent), hypotonia and muscle weakness, growth delay, exercise intolerance, cardiolipin abnormalities, and 3-methylglutaconic aciduria. Barth Syndrome is believed to growth anomalies have been widely reported in BTHS, there is a paucity of research on the contribution of catabolic/anabolic processes, the influence of inflammation and the potential link to alterations in growth factor levels in BTHS patients. Increased levels of Tumor Necrosis Factor alpha (TNF-α) have been shown to suppress the AKT/mTOR (mammalian target of rapamyosin) pathway, a crucial pathway for regulating
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