Lipid profile in Noonan syndrome and related disorders: trend by age, sex and genotype

BackgroundRASopathies are developmental disorders caused by dysregulation of the RAS-MAPK signalling pathway, which contributes to the modulation of multiple extracellular signals, including hormones and growth factors regulating energetic metabolism, including lipid synthesis, storage, and degradation.Subjects and methodsWe evaluated the body composition and lipid profiles of a single-centre cohort of 93 patients with a molecularly confirmed diagnosis of RASopathy by assessing height, BMI, and total cholesterol, HDL, triglycerides, apolipoprotein, fasting glucose, and insulin levels, in the context of a cross sectional and longitudinal study. We specifically investigated and compared anthropometric and haematochemistry data between the Noonan syndrome (NS) and Mazzanti syndrome (NS/LAH) groups.ResultsAt the first evaluation (9.5 ± 6.2 years), reduced growth (-1.80 ± 1.07 DS) was associated with a slightly reduced BMI (-0.34 DS ± 1.15 DS). Lipid profiling documented low total cholesterol levels (< 5th percentile) in 42.2% of the NS group; in particular, in 48.9% of PTPN11 patients and in 28.6% of NS/LAH patients compared to the general population, with a significant difference between males and females. A high proportion of patients had HDL levels lower than the 26th percentile, when compared to the age- and sex-matched general population. Triglycerides showed an increasing trend with age only in NS females. Genotype-phenotype correlations were also evident, with particularly reduced total cholesterol in about 50% of patients with PTPN11 mutations with LDL-C and HDL-C tending to decrease during puberty. Similarly, apolipoprotein A1 and apolipoprotein B deficits were documented, with differences in prevalence associated with the genotype for apolipoprotein A1. Fasting glucose levels and HOMA-IR were within the normal range.ConclusionThe present findings document an unfavourable lipid profile in subjects with NS, in particular PTPN11 mutated patients, and NS/LAH. Further studies are required to delineate the dysregulation of lipid metabolism in RASopathies more systematically and confirm the occurrence of previously unappreciated genotype-phenotype correlations involving the metabolic profile of these disorders

Celiac Disease Negatively Influences Lipid Profiles in Youngest Children With Type 1 Diabetes: Effect of the Gluten-Free Diet

The association between low HDL cholesterol (HDL-C) concentrations and increased cardiovascular risk is well established. Low HDL-C levels were found in subjects with type 1 diabetes (T1D) who presented complications and in untreated subjects with celiac disease (CD). The association between TID and CD might therefore enhance this lipid abnormality and accelerate the atherosclerotic process

Whole lipid profile and not only HDL cholesterol is impaired in children with coexisting type 1 diabetes and untreated celiac disease.

AIMS: Low HDL cholesterol (HDL-C) levels have been described in patients with coexisting type 1 diabetes mellitus (T1DM) and celiac disease (CD). Data on other possible lipid abnormalities that could further increase cardiovascular risk in these patients are scarce and incomplete. Aim of this retrospective multicenter study was to evaluate whole lipid profiles, besides HDL-C, in children with T1DM associated with biopsy-proven CD, and to investigate the influence of age and degree of adherence to gluten-free diet (GFD) on lipid changes. METHODS: A total of 261 children with both T1DM and CD were enrolled. Serum lipid profiles at CD diagnosis were compared with those after 1 year of GFD and with those of 224 matched children with T1DM alone. The adherence to GFD was judged by means of CD-related antibodies. RESULTS: At CD diagnosis, children with T1DM + CD showed higher LDL cholesterol (LDL-C) compared to children with T1DM alone. Gluten withdrawal failed to normalize LDL-C levels, not even in completely adherent individuals. HbA1c values were not influenced by GFD. The youngest children were characterized at diagnosis by lower levels of total cholesterol and on treatment by a greater decrease in triglycerides levels. CONCLUSIONS: An unfavorable lipid profile, characterized not only by low HDL-C levels but also by high LDL-C values, may increase the risk of cardiovascular disease in children with T1DM and untreated CD. Therefore, a strict gluten-free diet is mandatory in these children, especially the youngest