A child with hyperferritinemia: Case report

Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare condition caused by mutations in the gene coding for the light chain of ferritin; it does not lead to iron overload, but it is associated with the risk of developing a bilateral nuclear cataract also in childhood. On the contrary, a raise of serum ferritin levels is a common finding in pediatrics. We describe here a case of HHCS that offers some interesting clues for the daily practice. Our patient is a 6 year old Italian boy who came to our attention after some time of diagnostic uncertainties because of persistently high levels of ferritin with no apparent cause. We were guided to the suspect of this syndrome by the family history (5 members with various degrees of cataract developed in first infancy). High levels of serum ferritin and specific genetic testing (mutation A37C) confirmed the diagnosis. This case underlines the need of considering rare genetic syndromes, including hereditary hyperferritinemia cataract syndrome, in the differential diagnosis of raised serum ferritin in children and the importance of paying attention to family history in considering a patient with isolated raised levels of serum ferritin

The difference of free light chains as a predictor of kidney damage in patients with Multiple Myeloma

Background: Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal expansion of plasma cells that can release monoclonal immunoglobulins (monoclonal component) or part of theme. Since 2001, the k and λ serum free light chains (sFLC) evaluation and their ratio (rFLC) have made up the laboratory analysis more sensitive and precise in MM patients. The role of rFLC has been widely studied and discussed and now it is validated in the literature. Instead, the value of free light chains difference (dFLC), especially in MM is less known yet. The aim of this study is to evaluate the relationship between the dFLC and the kidney damage parameters in patients with MM, in comparison with the rFLC value. Methods: We conducted a retrospective population-based study on 58 MM patients and we individuated two groups obtained considering the measures of dFLC and rFLC in relation to abnormal and normal values of some renal function markers, such us Bence-Jones proteinuria (BJ), albuminuria, proteinuria and serum creatinine. The Mann-Whitney test was used to test the difference between two independent samples. Results: We observed a significant greater mean score of dFLC in patients with abnormal levels of BJ (2322.91>297.47, p=0.0001), albuminuria (2650.61>671.37, p=0.0016) and proteinuria (2327.19>593.14, p= 0.0025), while there was no significant difference for serum creatinine (1636.18<1870.85, p=0.994). Instead, no differences were observed for the rFLC parameter. Conclusion: The data obtained allow us to conclude that dFLC can be considered a potential predictor of renal damage in MM patients, even better than rFLC

The relationship between personality traits and individual factors with perinatal depressive symptoms: a cross-sectional study

Background: Pregnancy is a crucial transition moment exposing women to potential mental health problems, especially depressive disturbances. Sociodemographic, pregnancy-related, and psychological factors have been related to depressive symptoms in the perinatal period. This study aims at (1) exploring personality and individual factors related with perinatal depressive symptoms, and (2) testing the mediating role of personality in the relation between characteristics of the woman's family of origin and depressive symptoms. Methods: Women in the perinatal period admitted to the gynecology unit for motherhood-related routine assessments (n = 241) were included in the study. A survey on individual sociodemographic, clinical, and pregnancy-related factors was administered, also including the Edinburgh Postnatal Depression Scale (EPDS) and the BIG-5 personality test. Results: Couple conflict and neuroticism were independent and directly correlated with EPDS total score (respectively: B = 2.337; p = .017; B = 0.303; p < .001). Neuroticism was a significant mediator of the relation between the presence of a psychiatric disorder diagnosis in participant's parents and the EPDS total score (indirect b = 0.969; BCCI95%=0.366-1.607). Conclusions: Couple relation and neuroticism traits are individual factors related to depressive symptoms in the perinatal period. The family of origin also plays an indirect role on perinatal depressive symptoms. Screening of these factors could lead to early recognition and more tailored treatments, ultimately leading to better outcome for the entire family

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The difference of free light chains as a predictor of kidney damage in patients with Multiple Myeloma

Background: Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal expansion of plasma cells that can release monoclonal immunoglobulins (monoclonal component) or part of theme. Since 2001, the k and λserum free light chains (sFLC) evaluation and their ratio (rFLC) have made up the laboratory analysis more sensitive and precise in MM patients. The role of rFLC has been widely studied and discussed and now it is validated in the literature. Instead, the value of free light chains difference (dFLC), especially in MM is less known yet. The aim of this study is to evaluate the relationship between the dFLC and the kidney damage parameters in patients with MM, in comparison with the rFLC value.Methods: We conducted a retrospective population-based study on 58 MM patients and we individuated two groups obtained considering the measures of dFLC and rFLC in relation to abnormal and normal values of some renal function markers, such us Bence-Jones proteinuria (BJ), albuminuria, proteinuria and serum creatinine. The Mann-Whitney test was used to test the difference between two independent samples. Results: We observed a significant greater mean score of dFLC in patients with abnormal levels of BJ (2322.91>297.47, p=0.0001), albuminuria (2650.61>671.37, p=0.0016) and proteinuria (2327.19>593.14, p= 0.0025), while there was no significant difference for serum creatinine (1636.18<1870.85, p=0.994). Instead, no differences were observed for the rFLC parameter.Conclusion:The data obtained allow us to conclude that dFLC can be considered a potential predictor of renal damage in MM patients, even better than rFLC

Genetic variants of TAS2R38 bitter taste receptor associate with distinct gut microbiota traits in Parkinson's disease: A pilot study

The non-tasting form of the bitter taste receptor, TAS2R38, has been shown as a genetic risk factor associated with the development of Parkinson's disease (PD). Specific taste receptors that are expressed in the lower gastrointestinal tract may respond to alteration in gut microbiota composition, detecting bacterial molecules, and regulate immune responses. Given the importance of brain-gut-microbiota axis and gene-environment interactions in PD, we investigate the associations between the genetic variants of TAS2R38 and gut microbiota composition in 39 PD patients. The results confirm that the majority of PD patients have reduced sensitivity to 6-n-propylthiouracil (PROP) and are carriers of at least one non-functional TAS2R38 AVI haplotype. Moreover, we found this correlation to be associated with a reduction in bacteria alpha-diversity with a predominant reduction of Clostridium genus. We hypothesised that the high frequency of the non-taster form of TAS2R38 associated with a diminuition of Clostridium bacteria in PD might determine a reduction in the activation of protective signalling-molecules useful in preserving gut homeostasis. This pilot study, by identifying a decrease in specific bacteria associated with a reduced sensitivity to PROP, adds essential information that opens new avenues of research into the association of PD microbiota composition and sensory modification

Further lowering of muscle lipid oxidative capacity in obese subjects after biliopancreatic diversion

A reduced lipid oxidative capacity is considered a risk factor for the development of obesity, but a further impairment of lipid oxidative capacity is observed after weight loss. We aimed to define the mechanisms underlying this phenomenon in skeletal muscle and in particular to study the mitochondrial and peroxisomal lipid oxidative pathways. Thus we measured intramyocellular triglyceride content (IMTG) and the expression of genes of lipid oxidation [peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase 1B, and acyl-coenzyme A (acyl-CoA) oxidase 1] and synthesis (acetyl-CoA carboxylase B) using RT-PCR analysis in muscle biopsies of morbidly obese patients before and after biliopancreatic diversion. Weight reduction significantly decreased IMTG while increasing insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Moreover, an increase in glucose and a decline in lipid oxidation, as assessed by respiratory chamber, were observed. Weight loss reduced the expression of peroxisome proliferator-activated receptor-alpha (-46.7%), carnitine palmitoyltransferase 1B (-43.1%), acyl-CoA oxidase 1 (-37.8%), and acetyl-CoA carboxylase B (-48.7%). Our results indicate that a defect of both peroxisomal and mitochondrial oxidative pathways at the muscular level may contribute to the reduced fat oxidation in obese subjects after biliopancreatic diversion. They also suggest that a depression of the de novo lipogenesis may account for IMTG depletion