UNASSIGNED: Xanthomas are skin swellings that are caused by the accumulation of cholesterol and lipids in the body. They are associated with lipid disorders, such as familial hypercholesterolemia (FH). FH is a rare genetic disorder, which is characterized mainly by high levels of low density lipoprotein cholesterol.
UNASSIGNED: The authors report a case of an 11-year-old female who had multiple swellings all over the body with the largest measuring 7×4×3 cm in diameter. These lesions were gradually increasing in size since 4 years. She was being bullied by her school colleagues because of swellings appearance. Clinical examination revealed multiple yellowish masses on the patient\'s elbows, knees, and buttocks which were painless, firm, and nontender. Laboratory tests revealed elevated levels of serum cholesterol (512 mg/dl) and low density lipoprotein cholesterol (469.2 mg/dl). Masses ultrasound showed similar echogenicity to upper and lower extremities subcutaneous fat. Incisional biopsy microscopic images revealed clusters of foam cells. These findings led to a diagnosis of Homozygous FH and she underwent surgery to remove the xanthomas on her elbows.
UNASSIGNED: Xanthomas are small, yellowish skin swellings that form due to the presence of high lipids. As they are typically painless and small, this could lead to a late treatment or misdiagnosis. Drugs, lifestyle changes, and surgery represent treatment plan options.
UNASSIGNED: Xanthomas can be the first indication of an underlying hypercholesterolemia problem and this case report highlights the importance of early diagnosis of Homozygous FH by providing the suitable management for this case in its early stages which can prevent developing serious complication.

BACKGROUND: Premature aortic involvement and comprehensive management strategies in familial hypercholesterolemia familial hypercholesterolemia (FH), a rare autosomal dominant genetic disorder, poses significant challenges due to its propensity for elevated low-density lipoprotein cholesterol, premature coronary heart disease, and vascular atherosclerosis.
METHODS: Unraveling Cardiovascular Complexities: A Striking Familial Hypercholesterolemia. This case study delves into a remarkable instance of FH in a 16-year-old female who presented with chest pain and worsening dyspnea. Diagnostic evaluation revealed distinct electrocardiographic changes, elevated troponin levels, and profound dyslipidemia. Remarkable findings on transthoracic echocardiography, computed tomography angiography, and catheterization prompted multidisciplinary interventions and demonstrated remarkable enhancements in ventricular function, mitral regurgitation, and aortic stenosis.
CONCLUSIONS: The case study underscores the urgency of comprehensive management strategies in confronting the myriad challenges of FH, emphasizing the value of early intervention, innovative therapies, and rigorous imaging modalities for unraveling the intricate cardiovascular manifestations of this condition.

UNASSIGNED: A certain level of low-density lipoprotein receptor activity is crucial for the efficacy of PCSK9i. Therapeutic strategies for familial hypercholesterolemia patients should consider drug efficacy, and genetic testing will be helpful.
UNASSIGNED: Familial hypercholesterolemia (FH) is a serious autosomal dominant disorder. Managing blood lipids in FH patients poses greater challenges for clinicians. Drug therapy may not always yield satisfactory results, particularly in individuals with low-density lipoprotein receptor (LDLR) negative mutations. Herein, we report a young female harboring an LDLR frameshift mutation. This patient developed xanthomas at 7 months old and underwent several years of treatment involving four classes of lipid-lowering drugs, including PCSK9i. However, the response to drug therapy was limited in this patient and eventually culminated in premature myocardial infarction. The efficacy of PCSK9i depends on the activity of LDLR. The inefficacy of PCSK9i may arise from the extensive mutations which leading to loss of LDLR activity. Therapy plans for these patients should take into account the efficacy of drug therapy. Early genetic testing is crucial for clinicians to make informed decisions regarding therapy options.

BACKGROUND: Familial hypercholesterolemia (MIM: PS143890) is a genetic disorder characterized by an increase in blood cholesterol. LDLR is one of the genes which their defect contributes to the disorder. Affected individuals may carry a heterozygous variant or homozygous/compound heterozygous variants and those with biallelic pathogenic variants present more severe symptoms.
METHODS: We report an Egyptian family with familial hypercholesterolemia. Both the proband and parents have the disorder while a sibling is unaffected. Exome sequencing was performed to identify the causal variant.
RESULTS: LINE-1 insertion in exon 7 of LDLR was identified. Both parents have a heterozygous variant while the proband has a homozygous variant. The unaffected sibling did not carry the variant.
CONCLUSIONS: This insertion may contribute to the high prevalence of hypercholesterolemia in Egypt and the finding underscores the importance of implementing mobile element insertion caller in routine bioinformatics pipeline.

Hypertriglyceridemia is one of the major causes of acute pancreatitis in addition to gallstones and alcohol use. These etiologies are often associated with underlying comorbidities. Acute pancreatitis secondary to hypertriglyceridemia is associated with an increase in clinical severity and further complications. We present a case of a 56-year-old man with a past medical history of hypertension, diabetes mellitus, and familial hypertriglyceridemia who was diagnosed with acute pancreatitis secondary to hypertriglyceridemia. The patient presented with 9/10 pressure across the abdomen radiating to the sternum. Labs revealed elevated triglyceride count > 8000 mg/dL and cholesterol > 705 mg/dL. Abdominal CT showed fat stranding along the anterior aspect of the pancreatic head. The patient was managed with IV fluids, nil per os (NPO), and statin management for hypertriglyceridemia. Seven days later, triglycerides decreased to 658 mg/dL, and abdominal pain resolved. This case highlights an unusual presentation of acute pancreatitis and demonstrates the importance of understanding the spectrum of etiologies for this condition.

Limited data have been reported on the use of proprotein convertase subtilisin/kexin type 9 (PCSK 9) inhibitors during pregnancy in women with familial hypercholesterolemia (FH). Here, we present the first case of initiating evolocumab (PCSK9 inhibitor) in a compound heterozygous FH mother. The patient was a 34-year-old primipara with severe dyslipidemia and a history of coronary artery bypass surgery. An elevated low-density lipoprotein cholesterol (LDL-C) level of 420 mg/dL was detected in the first trimester and persistently increased throughout pregnancy. Evolocumab was administered at 31 and 35 weeks of gestation, showing a positive effect on stabilizing LDL-C levels. Planned delivery with labor analgesia was performed at 38 + 4 weeks. Both the mother and infant were discharged without any notable complications. Hence, evolocumab, an IgG2 monochromatic antibody with little placental permeability, may be an alternative medication with limited influence on infants. Further studies are needed to assess the safety of evolocumab administration during pregnancy.

A 28-year-old woman with autosomal dominant familial hypercholesterolemia (FH) with a probable coexistent polygenic contribution causing very high low-density lipoprotein-cholesterol (LDL-C) levels, started therapy with the proprotein convertase subtilisin/kexin type 9-inhibitor (PCSK9i) alirocumab, in addition to high-intensity statin plus ezetimibe. Forty-eight hours after the second injection of alirocumab, the patient developed a painful palpable injection site reaction (ISR) that recurred after the third administration of the drug. Treatment was then switched to evolocumab, another PCSK9i, but the patient had an ISR with similar features. The most conceivable cause of the ISR was a cell-mediated hypersensitivity reaction to polysorbate, an excipient contained in both drugs. Although ISR after PCSK9i administration is usually transient and does not compromise the continuation of treatment, in this case the recurrence of such side effect in an exacerbated way led to treatment withdrawal, with a subsequent re-exposure to increased cardiovascular (CV) risk. As soon as it became available in clinical practice, the patient started treatment with inclisiran, a small interfering RNA targeting hepatic PCSK9 synthesis. No adverse events were reported after inclisiran administration and LDL-C levels decreased significantly, confirming the evidence that this innovative approach to hypercholesterolemia is a safe and effective resource in patients at high CV risk who cannot achieve LDL-C goal with conventional lipid-lowering therapies and antibody-based PCSK9i.

BACKGROUND: Familial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool.
OBJECTIVE: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting.
METHODS: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the \"think-aloud\" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool.
RESULTS: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023.
CONCLUSIONS: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients\' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease.
UNASSIGNED: DERR1-10.2196/47911.

Familial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background.
We treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister.
Patients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.

The effect of SARS-CoV-2 infection in blood lipids of homozygous familial hypercholesterolemia (HoFH) has not been explored.
We report a case of a 43-year-old male patient with -/-LDLR HoFH with previous history of premature coronary artery disease, coronary artery bypass graft (CABG) and surgical repair of aortic valve stenosis. He presented with an abrupt decrease of his blood lipid levels during acute infection with SARS-CoV2 and subsequently a rebound increase above pre-infection levels, refractory to treatment including LDL-apheresis, statin, ezetimibe and lomitapide up-titration to maximum tolerated doses. Markers of liver stiffness were closely monitored, increased at 9 months and decreased at 18 months after the infection. Potential interactions of hypolipidemic treatment with the viral replication process during the acute phase, as well as therapeutic dilemmas occurring in the post infection period are discussed.