The Importance of Genetic Testing for Familial Hypercholesterolemia: A Pediatric Pilot Study.

Background and Objectives: Familial hypercholesterolemia (FH) is a genetic disease that is massively underdiagnosed worldwide. Affected patients are at high risk of cardiovascular events at young ages. Early intervention in childhood could help prevent heart attacks and cerebral strokes in these patients. Materials and Methods: We conducted an interventional study including 10 patients that previously underwent genetic testing for familial hypercholesterolemia. These patients received lifestyle and diet recommendations that they followed for a year before being reevaluated. Results: Patients with negative genetic testing were able to achieve lower levels in their lipid panel values compared to the patients with positive genetic testing, with lifestyle changes alone. LDL-cholesterol levels decreased by 18.5% in patients without FH while patients genetically confirmed with FH failed to achieve lower LDL-cholesterol levels without medication. Conclusions: Genetic testing for FH is not always part of screening algorithms for FH. Some studies even advise against it. Our study proved the importance of genetic testing for FH when suspecting this disorder and choosing the treatment course for patients.

Dyslipidemia in Pediatric Patients: A Cross-Sectional Study.

There is an increasing interest in dyslipidemia in adult patients since it is known to contribute to early cardiovascular disease. Often, dyslipidemia starts in childhood, and it is associated with aggravating lifestyle choices concerning eating habits, such as the tendency to consume processed food and fast food, as well as the tendency to be more and more sedentary. We conducted a retrospective cross-sectional study describing the prevalence of dyslipidemia in a single medical center in Romania and the associated pathology. We evaluated all lipid profiles that were ordered in our clinic over nine years. We included 2413 patients that were evaluated in our clinic in the timeframe 2011-2020. Out of them, 18.23% had high values for LDL-cholesterol. More than a quarter (25.91%) were diagnosed with obesity. 11.37% of the patients with high LDL-cholesterol levels had various metabolic disorders including primary dyslipidemia. A small number of patients with hypercholesterolemia had thyroid disorders (4.10%). Patients with high LDL-cholesterol had various diagnoses ranging from metabolic to neurologic disorders, keeping in mind that there are multiple pathologies that can lead to dyslipidemia. Evaluating children for dyslipidemia is at hand for medical professionals. Screening for dyslipidemia in children would provide the opportunity to prevent rather than treat cardiovascular events.

X-Linked agammaglobulinemia in a child with Klinefelter's syndrome.

Bruton's agammaglobulinemia is a rare X-linked humoral immunodeficiency manifesting with recurrent bacterial infections early in life. Klinefelter's syndrome caused by an additional X chromosome is the most common sex chromosome disorder. A previously unreported association of these two conditions is described here.

Genetic Testing for Familial Hypercholesterolemia in a Pediatric Group: A Romanian Showcase.

Familial hypercholesterolemia (FH) is a genetic disease marked by high levels of LDL-cholesterol. This condition has long-term clinical implications, such as cardiovascular events, that are evident during adult life. Here, we report on a single-center cross-sectional showcase study of genetic testing for FH in a Romanian pediatric group. Genetic testing for FH was performed on 20 Romanian pediatric patients, 10 boys and 10 girls, admitted with LDL-cholesterol levels over 130 mg/mL to the National Institute for Mother and Child Health "Alesssandrescu-Rusescu" in 2020. Genetic testing was performed using the Illumina TruSight Cardio panel. We identified pathogenic/likely pathogenic variants that could explain the phenotype in 5/20 cases. The involved genes were LDLR and APOB. Clinical signs that suggest the diagnosis of FH are scarce for the pediatric patient, although it can be diagnosed early during childhood by lipid panel screening. Prevention could prove lifesaving for some of these patients.

Lipid profile pattern in pediatric overweight population with or without NAFLD in relation to IDF criteria for metabolic syndrome: a preliminary study.

BACKGROUND AND AIMS: The aim of this study is to assess the lipid profile pattern of pediatric overweight and/or obese patients with Non-Alcoholic Fatty Liver Disease (NAFLD) in relation to IDF Consensus Criteria for Metabolic Syndrome (MetS). MATERIAL AND METHODS: We conducted a cross-sectional preliminary study on 45 consecutive pediatric patients. Overweight or obese children aged from 3 to 18 years were included. Standardized measurement of blood pressure and anthropometric parameters were performed. Biological evaluation included inflammatory status, lipid profile, glycemic profile, full blood count and liver function tests. Abdominal ultrasound was performed in all patients. RESULTS: Prevalence of MetS was 44.4%. A number of 21 patients (46.7%) had NAFLD. MetS patients had higher risk for NAFLD (OR = 9.5, 95% CI = 2.42-37.24). Also patients with positive familial history of type 2 diabetes had a 6.61 fold higher risk for NAFLD (OR = 6.61, 95% CI = 1.74-25.1). We performed a subgroup analysis in patients under ten years old. Patients under the age of ten which had both NAFLD and MetS met more frequently the hypertriglyceride criterion. After adjusting for age and MetS presence, triglyceride levels independently associated with NAFLD (adjusted R square = 0.46, unstandardized B coefficient = 34.51, 95% CI = 4.01-65.02, p = 0.02). CONCLUSION: NAFLD obese patients had higher prevalence of MetS, higher BMI and particular lipid profile pattern. Triglyceride levels independently associated with NAFLD after adjusting for age and MetS presence. According to our findings we suggest early triglyceride testing (even below the age of ten) in selected patients.

Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: a cohort study.

Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.