Premature subclinical atherosclerosis in children and young adults with juvenile idiopathic arthritis.:A review considering preventive measures

Many studies show that Juvenile Idiopathic Arthritis (JIA) is associated with early subclinical signs of atherosclerosis. Chronic inflammation per se may be an important driver but other known risk factors, such as dyslipidemia, hypertension, insulin insensitivity, a physically inactive lifestyle, obesity, and tobacco smoking may also contribute substantially. We performed a systematic review of studies through the last 20 years on early signs of subclinical atherosclerosis in children and adolescents with JIA with the purpose of investigating whether possible risk factors, other than inflammation, were considered. We found 13 descriptive cross sectional studies with healthy controls, one intervention study and two studies on adults diagnosed with JIA. Only one study addressed obesity, and physical activity (PA) has only been assessed in one study on adults with JIA and only by self-reporting. This is important as studies on PA in children with JIA have shown that most patients are less physically active than their healthy peers, and as physical inactivity in several large studies of normal schoolchildren is found to be associated with increased clustering of risk factors for cardiovascular disease. It is thus possible that an inactive lifestyle in patients with JIA is an important contributor to development of the subclinical signs of atherosclerosis seen in children with JIA, and that promotion of an active lifestyle in childhood and adolescence may diminish the risk for premature atherosclerotic events in adulthood

Reduced physical activity in children and adolescents with Juvenile Idiopathic Arthritis despite satisfactory control of inflammation.

Background: Vascular health is of concern in patients with Juvenile Idiopathic Arthritis (JIA) since Rheumatoid Arthritis (RA) epidemiologically has a well-described association with premature development of atherosclerosis. Chronic inflammation with persisting systemic circulating inflammatory proteins may be a cause of vascular damage, but general physical inactivity could be an important contributor. Pain and fatigue are common complaints in patients with JIA and may well lead to an inactive sedentary lifestyle. For this reason we assessed the physical activity (PA) objectively in patients with moderate to severe Juvenile Idiopathic Arthritis (JIA) in comparison with gender and age matched healthy schoolchildren, and looked for associations between PA and features of JIA. Methods: One hundred thirty-three patients, 7–20 years of age, participated. Disease activity, disability, functional ability, and pain were assessed and PA was measured by accelerometry through 7 days and compared to PA in age- and gender-matched healthy schoolchildren. Results: We found a significantly lower level of PA in patients compared to gender- and age-matched healthy schoolchildren both in average activity (counts per minute, cpm) (475.6 vs. 522.7, p = 0.0000018) and in minutes per day spent with cpm >1500 (67.9 vs. 76.4, p = 0.0000014), with cpm >2000 (moderate physical activity) (48.4 vs. 52.8, p = 0.0001, and with cpm >3000 (high physical activity) (24.7 vs. 26.5, p = 0.00015). A negative association (β = −0.213, p = 0.014) between active disease in weight bearing joints and high physical activity remained the only significant association between disease related factors and PA. Of the girls 19 % and of the boys 45 % (vs. 39 % and 61 % in the reference group) met standards set by Danish Health Authorities for daily PA in childhood. Conclusion: Children and adolescents with JIA are less physically active than their healthy peers and less active than recommended for general health by the Danish Health Authorities. This is not explained by pain or objective signs of inflammation. When inflammation has been curbed, restoration of an active healthy lifestyle should be highly prioritized

Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations

Disorders caused by defects in the mitochondrial translation system are clinically and genetically heterogeneous. The elongation phase of mitochondrial protein synthesis requires, among many other components, three nuclear-encoded elongation factors: EFTu (TUFM; 602389), EFTs (TSFM; 604723), and EFG1 (GFM1; 606639). Mutations have been identified in the genes encoding all three elongation factors, and they result in combined respiratory chain deficiencies and severe phenotypes with an early fatal outcome. So far, only eleven patients have been reported with mutations in GFM1. Here we describe an additional three patients with novel GFM1 mutations. Our results confirm the tissue-specific effect of GFM1 mutations, since we found only slightly decreased respiratory chain enzyme activities in muscle and fibroblasts, but a severe deficiency in the liver. Hence, a thorough biochemical evaluation is important to guide genetic investigation in patients suspected for a mitochondrial disorder