Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first decades of life. In cases of neglected treatment, young patients have a risk of death from coronary diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders. The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation was observed in exon 3 of the low-density lipoprotein receptor (LDLR): c. 295 G>A (p.Glu99Lys). Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it emphasizes the need for increased clinical awareness among healthcare providers, as early detection and intervention are important for improving outcomes, particularly in pediatric patients with this rare genetic disorder.

Background: The comparative effects of pharmacological treatment, bariatric surgery, and diet on insulin resistance (IR) remain unclear. Aim: To study the comparative effects of the methods on IR: pharmacologic, bariatric surgery, and very-low-calorie diet (VLCD) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Methods: Design: a 90-day prospective, multicenter, comparative clinical trial including 130 adult patients divided into three groups: Drug, Surgery, and VLCD. Endpoints: HOMA-IR; weight loss; and HbA1c, systolic/diastolic blood pressure (SBP/DBP). Results: At 90 days, weight loss in the Surgery (−19.8%) and VLCD groups (−17.4%) was significant (p < 0.0001), while in the Drug group, the loss was insignificant (−6.5%; p = 0.06). SBP/DBP in the Drug group decreased by −9.5% (p = 0.0002) and −4.1% (p = 0.09), respectively. SBP/DBP in the Surgery group decreased by −13.6% and −10.6%, respectively (p < 0.001), and in the VLCD group, by −23.3% and 21.3%, respectively (p < 0.0001). HOMA-IR in Drug, Surgery, and VLCD groups decreased by −42.2% (p = 0.004), −87.6% (p < 0.0001), and −88.7% (p < 0.0001), respectively. In the Drug group, HOMA-IR did not reach the normal level. Correlation-regression analysis revealed a direct correlation between weight loss and a decrease in HOMA-IR (r = 0.526; F = 33.2, p < 0.0001). HOMA-IR decreases by 65% if weight decreases by 10%; if weight decreases by 25%, then HOMA-IR decreases by 83%. Conclusions: HOMA-IR was associated with weight loss: the greater the weight loss, the lower the HOMA-IR. Weight loss leads to a reduction in the need for antidiabetic/antihypertensive drugs in patients with T2DM and hypertension.

Background: Pediatric epilepsy is a clinically and genetically heterogeneous group of disorders, particularly in early-onset and syndromic presentations. Data integrating molecular findings with detailed clinical phenotyping remain limited in Kazakhstan and Central Asia. Methods: We conducted a retrospective, single-center, clinically selected, referral-based case series study of 31 pediatric patients evaluated at a tertiary center in Kazakhstan for epilepsy or epilepsy-associated neurodevelopmental disorders and found to have clinically relevant or potentially relevant genetic findings. Clinical records were reviewed for demographics, age at seizure onset, seizure semiology, developmental profile, EEG, MRI, extra-neurological features, treatment response, and family history. Variants were interpreted using ACMG-based criteria, and inheritance/segregation data were incorporated where available. Results: The cohort included 15 males and 16 females. Median seizure onset was 5.0 months (IQR 2.0–13.0), and 22/31 patients (71.0%) presented within the first year of life. Developmental delay/intellectual impairment was observed in 20/31 cases (64.5%), speech delay in 17/31 (54.8%), motor delay in 15/31 (48.4%), and hypotonia in 12/31 (38.7%). Variants were identified in 23 genes, including several variants with limited or no prior support in ClinVar or peer-reviewed reports. Ion channelopathies were the largest mechanistic group (12/31, 38.7%), followed by mitochondrial/metabolic disorders (6/31, 19.4%), mTOR pathway disorders (5/31, 16.1%), and neurodevelopmental/chromatin/transcriptional disorders (4/31, 12.9%). SCN1A was the most recurrent gene (8/31, 25.8%) and showed a broad phenotypic continuum from Dravet-compatible to non-Dravet presentations. EEG and MRI abnormalities were common and often syndromic in pattern. Treatment response was frequently partial or poor, although selected genotype-linked treatment observations were noted in PRRT2 (carbamazepine), PNPO (pyridoxine), and one SCN1A case (stiripentol). Conclusions: This study expands the clinicogenetic characterization of pediatric epilepsy cases with clinically relevant or potentially relevant genetic findings in Kazakhstan and highlights the value of integrated molecular, phenotypic, and segregation analysis in underrepresented populations.

Monogenic epilepsies and developmental and epileptic encephalopathies are biologically heterogeneous, and evidence for plant-derived interventions ranges from ethnopharmacology to randomized clinical trials. This review critically maps that evidence using a four-level genotype-relevance framework while separating antiseizure, neuroprotective, mechanistic, and clinical endpoints. Highly purified cannabidiol (CBD) has the strongest evidence chain: antiseizure activity in Scn1a-based Dravet models is complemented by randomized clinical efficacy at the syndrome level. However, current trial evidence does not establish an SCN1A-genotype-specific treatment response. β-Caryophyllene has direct preclinical evidence in a genetically relevant Dravet model. Luteolin has direct CDKL5-model evidence for reducing microglial overactivation and improving neuronal and neurodevelopmental outcomes, but seizure-frequency or video-EEG efficacy in CDKL5 deficiency disorder has not been demonstrated. Curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), quercetin, and sulforaphane are supported mainly by non-genetic seizure models and therefore remain mechanistically plausible candidates rather than validated treatments for monogenic epilepsy. Medicinal plants, crude extracts, standardized preparations, and isolated compounds are considered separately. Translational prioritization should require a reproducible genotype-associated secondary phenotype, clinically meaningful functional outcomes, achievable systemic and brain exposure, acceptable safety and drug-interaction profiles, and reproducible formulation. Plant-derived compounds should therefore be viewed as potential adjuncts to established antiseizure, syndrome-specific, and gene-directed therapies rather than substitutes.

Background: The comparative effects of pharmacological treatment, bariatric surgery, and diet on insulin resistance (IR) remain unclear. Aim: To study the comparative effects of the methods on IR: pharmacologic, bariatric surgery, and very-low-calorie diet (VLCD) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Methods. Design: a 90-day prospective, multicenter, comparative clinical trial including 130 adult patients divided in three groups: Drug, Surgical, and VLCD groups. Endpoints: HOMA-IR; weight loss; HbA1c, systolic/diastolic blood pressure (SBP/DBP). Results. At 90 days, weight lost in Surgery (-19.8%) and VLCD groups (-17.4%) (P< 0.0001), while in Drug group the loss was unsignificant (-6.5%; P=0.06). SBP/DBP in Drug group decreased by -9.5% (P=0.0002) and -4.1% (P=0.09), respectively. SBP/DBP in: Surgical group decreased by -13.6% and -10.6%, respectively (P< 0.001); VLCD group -23.3% and 21.3%, respectively (P< 0.0001). HOMA-IR in Drug, Surgery and VLCD groups decreased by -42.2% (P=0.004), -87.6% (P< 0.0001), and -88.7% (P< 0.0001), respectively. In Drug group HOMA-IR did not reach normal level. Correlation-regression-analysis revealed a direct correlation between weight-loss and a decrease in HOMA-IR (r=0.526; F=33.2, P< 0.0001). HOMA-IR decreases by 65% if weight decreases by 10%; if weight decreases by 25%, then HOMA-IR decreases by 83%. Conclusions. HOMA-IR was associated with weight loss: the greater the weight loss, the lower HOMA-IR. Weight loss leads to reduce the need for antidiabetic/antihypertensive drugs in the patients.