Colitis in a patient with familial Mediterranean fever: Is it Crohn's disease or ulcerative colitis?

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever.

Lipoprotein apheresis: an established therapeutic modality for homozygous familial hypercholesterolemia patients refractory to PCSK9 inhibitors: a case report and literature review.

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12-14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1-2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

The Ser434Phe Androgen Receptor Gene Mutation Does Not Affect Fertility but is Associated with Increased Prolactin.

Introduction: Prolactin is a hormone secreted by the anterior pituitary gland essential for lactation. Non-physiological hyperprolactinemia characterized by serum prolactin levels exceeding 20 ng/mL in men and 25 ng/mL in women, often results from medication use or pituitary gland tumors. In a minority of cases, the cause of hyperprolactinemia remains unknown despite clinical investigations. Familial idiopathic hyperprolactinemia may stem from mutations in genes encoding prolactin (PRL) and its receptor (PRLR). Methods: This study investigated genetic polymorphisms in PRL and PRLR genes using polymerase chain reaction (PCR) and Sanger sequencing in three sisters affected by familial idiopathic hyperprolactinemia. No mutations were found in these genes, prompting whole exome sequencing (WES) of the proband to identify other potentially involved genes. Results: WES revealed a heterozygous missense substitution c.1301C>T (p.Ser434Phe) in the androgen receptor (AR) gene. Next-generation sequencing (NGS) for the AR gene confirmed that the proband and her two affected sisters, along with three asymptomatic sisters, were all heterozygous carriers of the mutation. Their father was hemizygous, while their mother had a normal genotype. Conclusion: The heterozygous missense mutation in the AR gene found in this family with familial idiopathic hyperprolactinemia is not yet explained. Hence, further research is warranted to elucidate the functional implications of this mutation on AR and its role in the pathogenesis of hyperprolactinemia.

Large-scale application of ClinGen-InSiGHT APC-specific ACMG/AMP variant classification criteria leads to substantial reduction in VUS.

Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUSs), APC-specific variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) based on the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). A streamlined algorithm using the APC-specific criteria was developed and applied to assess all APC variants in ClinVar and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) international reference APC Leiden Open Variation Database (LOVD) variant database, which included a total of 10,228 unique APC variants. Among the ClinVar and LOVD variants with an initial classification of (likely) benign or (likely) pathogenic, 94% and 96% remained in their original categories, respectively. In contrast, 41% ClinVar and 61% LOVD VUSs were reclassified into clinically meaningful classes, the vast majority as (likely) benign. The total number of VUSs was reduced by 37%. In 24 out of 37 (65%) promising APC variants that remained VUS despite evidence for pathogenicity, a data-mining-driven work-up allowed their reclassification as (likely) pathogenic. These results demonstrated that the application of APC-specific criteria substantially reduced the number of VUSs in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalizable model for other gene- or disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUSs that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.

Complex Coronary Artery Lesions in a Young Woman With an Acute Myocardial Infarction and Genetically Confirmed Familial Hypercholesterolemia: A Case Report and Literature Review From a Developing Country.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood from an incredibly early age. This condition leads to the early development of atherosclerotic arterial diseases, which can manifest even in the first few decades of life. Mutations in genes related to the LDL receptor (LDL-R), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) are the main molecular mechanisms causing familial hypercholesterolemia. This case involves a 44-year-old Vietnamese female who presented at the emergency department with chest pain and was diagnosed with acute myocardial infarction (AMI) complicated by cardiogenic shock. Clinical signs and an elevated LDL-C level pointed to prolonged exposure to high cholesterol. A Dutch Lipid Clinic Network (DLCN) score of 10 further supported the diagnosis of FH. The reverse T-stenting and small protrusion (TAP) technique was selected and successfully employed to stent the LMCA, left anterior descending artery (LAD) and left circumflex artery (LCx). This technique was chosen due to its simplicity and rapid execution, making it particularly suitable in situations of cardiogenic shock where time-consuming procedures should be avoided. Genetic testing confirmed a heterozygous pathogenic mutation in the LDL-R gene, corroborating the clinical diagnosis of FH. The patient's condition has gradually stabilized, and they have been discharged from the hospital. The patient is currently being monitored as an outpatient at the cardiology clinic. This case emphasizes the importance of considering FH in patients with premature cardiovascular events by applying the clinical diagnostic criteria and confirming by genetic analysis. It also highlights advanced interventional techniques for managing complex coronary lesions, such as reverse TAP.

Two different mutational types of familial gastrointestinal stromal tumors: Two case reports.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and cases of GISTs tend to be of the disseminated type, with a global incidence of 10 to 15 cases/million each year. The rarer familial GISTs, which often represent a population, differ in screening, diagnosis, and treatment. Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs. However, whether the same genetic family has different phenotypes has not been reported. CASE SUMMARY: We report two cases of rare GISTs in the same family: A male patient with the V561D mutation in exon 12 of the PDGFRA gene, who has been taking the targeted drug imatinib since undergoing surgery, and a female patient diagnosed with wild-type GIST, who has been taking imatinib for 3 years since undergoing surgery. The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy, and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease. CONCLUSION: Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

Transitioning Adolescents and Young Adults with Lipid Disorders to Adult Health Care.

PURPOSE OF REVIEW: Pediatric healthcare providers have increasingly become aware of the need for timely and informative transition of adolescents and young adults with chronic medical conditions such as diabetes and cystic fibrosis. However, there is paucity of published data on the importance of and most effective way to transition youth with lipid disorders who are at increased risk of premature cardiovascular disease. RECENT FINDINGS: Evidence shows that atherosclerosis begins at a young age. However, there are no guidelines on the transition of adolescents and young adults with dyslipidemia. In addition, there are conflicting guidelines for lipid management in children versus adults, despite advances in medical pharmacotherapies for dyslipidemia. The lack of guidelines for transition and discordant recommendations for management of this vulnerable population places young adults at-risk for worsening of their underlying disease, and premature cardiovascular events.

Olezarsen and Plozasiran in Dyslipidemia Management: A Narrative Review of Clinical Trials.

Cardiovascular diseases are a worldwide known cause of mortality, often due to dyslipidemia and other modifiable and non-modifiable factors. Rare genetic conditions such as familial chylomicronemia are underdiagnosed and mismanaged. Traditional lipid-lowering therapies, such as statins, often have limitations, such as adverse effects and suboptimal lipid control in certain patient populations. Olezarsen and Plozasiran, as emerging therapies, offer potential benefits by targeting specific pathways involved in lipid metabolism. The asymptomatic presentation and high mortality rate warrant novel agents that can manage dyslipidemia. In this article, olezarsen and plozasiran are thoroughly reviewed. From clinical trials, plozasiran significantly improved non-HDL cholesterol levels, highlighting its comprehensive lipid-modifying effects. Olezarsen also demonstrated remarkable efficacy in reducing fasting triglycerides from baseline levels. Utilizing these medications for primary and secondary prevention of atherosclerotic cardiovascular diseases can significantly reduce the global burden of cardiovascular disease and its complications. The review discusses the therapeutic effects of Olezarsen and Plozasiran in managing dyslipidemia, especially familial chylomicronemia syndrome (FCS). While traditional treatments like lifestyle modifications and statins are common, novel antisense oligonucleotides such as Olezarsen and Plozasiran have significant modulatory effects on apolipoproteins, disrupting specific genes involved in lipid metabolism.

BRCA2 mutations in familial breast cancer with prostate cancer: a case report and literature review.

Prostate cancer (PCa) is the second most common tumor in men globally. Its etiology has been attributed to multiple factors, including age and ethnicity, with family history identified as a significant risk factor. The role of family history in prostate cancer risk appears to be more extensive than previously thought, with evidence suggesting that prostate cancer and breast cancer may occur concurrently within families. BRCA2 mutations have been linked to an increased risk of prostate cancer, particularly in patients diagnosed with early-onset disease. It is estimated that BRCA2 mutations account for approximately 5% of familial prostate cancer cases. It is noteworthy that cases of prostate cancer in patients with BRCA2 mutations are rare in clinical practice. Here we report a case of prostatitis carcinoma with a mutation in the BRCA2 gene in a patient who underwent robotic-assisted radical prostatectomy for prostatitis carcinoma after medication was not effective. Genetic testing of him, his son, and his daughter showed that they all had mutations in this gene, and it is noteworthy that the type of BRCA2 mutation in his son has never been reported before, which is rare in clinical practice.

A familial case of aortic dilatation with p.Tyr470Cys in TGFBR2 in which the phenotype included only vascular lesions.

Hereditary connective tissue diseases have different risks of aortic dissection depending on the causative gene. We report a family with no extravascular phenotype and a clinical diagnosis of familial thoracic aortic aneurysm and dissection, but genetic testing confirmed p.Tyr470Cys in TGFBR2, which is typically the responsible gene for Loeys-Dietz syndrome. Validation of the clinical diagnosis by genetic testing is warranted.

Challenges in the management of familial hypercholesterolemia: a case report.

Background: Familial hypercholesterolemia (FH) is a serious genetic condition that results in abnormally high levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream, significantly increasing the risk of early onset of cardiovascular disease. The heterozygous form of FH (HeFH) is widespread, affecting around 1 in 500 people worldwide. Case report: In this clinical report, we present the case of a patient who suffers from HeFH due to a mutation in the LDL receptor (LDLR) gene. A woman exhibited intolerance to statin therapy and did not attain adequate reduction in low-density lipoprotein cholesterol (LDL-C) levels on ezetimibe monotherapy. Genetic testing confirmed the presence of a pathogenic variant for FH with the deletion of exons 7-14. The administration of alirocumab (a dose of 150 mg sc) as the primary therapy did not exhibit the desired therapeutic outcome. Consequently, the patient was given inclisiran therapy (a dose of 284 mg sc), which significantly reduced LDL cholesterol levels after 3 months of treatment and during the 1-year follow-up. Conclusion: Inclisiran therapy has shown promising results for individuals with HeFH who experience statin intolerance. This therapy works by using a small interfering RNA (siRNA) to target the mRNA of proprotein convertase subtilisin/kexin type 9 (PCSK9), which leads to a significant reduction of LDL-C levels. This approach can be an alternative for patients without significant reductions in LDL-C levels with PCSK9 inhibitor therapy. For HeFH patients with limited treatment options due to statin intolerance and genetic mutations, inclisiran can represent a promising therapeutic option.

An autopsy report of a long-survival case of familial amyotrophic lateral sclerosis with SOD1 G93S gene mutation: Lack of SOD1-positive inclusion in the remaining neurons.

We describe the case of a 70-year-old Japanese man with familial amyotrophic lateral sclerosis (fALS) associated with a p.Gly93Ser mutation in the copper/zinc superoxide dismutase (SOD1) gene. This mutation is one of the relatively rare SOD1 mutations, with only one previous autopsy report, and is known for its longer disease duration. As previously reported, the patient had weakness in the lower limbs at age 33, followed by dysphagia, dysesthesia in the lower limbs, and autonomic dysfunction. He required mechanical ventilation at age 44 and died of acute pancreatitis at age 70. Neuropathologically, multisystem degeneration was observed beyond lesions typical of familial ALS with posterior column involvement. In addition, there was no SOD1-positive inclusion in the remaining motor neurons. The absence of SOD1-positive inclusion is a rare feature observed predominantly in long survival cases with SOD1 gene mutations. We hypothesize that the considerably lower amount of abnormal SOD1 protein in the motor neuron cells might explain our patient's extraordinarily long clinical course.

Murdered Elder Indigenous Women and Legal Outcomes.

This qualitative descriptive analysis examines 33 cases of missing and murdered Indigenous women aged 50 years and older. The cases encompassed single murders, multiple murders, and mass stabbing events. The study found that the offender was known and/or identified in the majority of cases, with a significant portion resulting in guilty pleas or jury convictions. However, a notable portion of cases remained unsolved or ended with the offender's suicide. Alcohol and/or illicit substance abuse was prevalent; known substance abuse history was identified in victim and/or offender for nearly 70% of cases. Most murders occurred off tribal land and were perpetrated by men, typically younger than their victims, with some form of relationship to them. Themes for the resolved cases varied, including familial violence, sexual violence, and financial gain. The findings underscore the need for intervention strategies such as addressing substance abuse in adolescence, intervening early in relationship conflicts, training law enforcement in elder sexual homicide investigations, and providing clinical care for mental illness in cases involving family and partners. Additionally, the study highlights the necessity for a national database to track homicides involving elder Indigenous women, facilitating more effective prevention and response efforts.

Familial cerebral amyloid disorders with prominent white matter involvement.

Familial cerebral amyloid disorders are characterized by the accumulation of fibrillar protein aggregates, which deposit in the parenchyma as plaques and in the vasculature as cerebral amyloid angiopathy (CAA). Amyloid ß (Aß) is the most common of these amyloid proteins, accumulating in familial and sporadic forms of Alzheimer's disease and CAA. However, there are also a number of rare, hereditary, non-Aß cerebral amyloidosis. The clinical manifestations of these familial cerebral amyloid disorders are diverse, including cognitive or neuropsychiatric presentations, intracerebral hemorrhage, seizures, myoclonus, headache, ataxia, and spasticity. Some mutations are associated with extensive white matter hyperintensities on imaging, which may or may not be accompanied by hemorrhagic imaging markers of CAA; others are associated with occipital calcification. We describe the clinical, imaging, and pathologic features of these disorders and discuss putative disease mechanisms. Familial disorders of cerebral amyloid accumulation offer unique insights into the contributions of vascular and parenchymal amyloid to pathogenesis and the pathways underlying white matter involvement in neurodegeneration. With Aß immunotherapies now entering the clinical realm, gaining a deeper understanding of these processes and the relationships between genotype and phenotype has never been more relevant.

Familial Nonautoimmune Hyperthyroidism Due to a TSH Receptor Gene Pathogenic Variant.

Familial nonautoimmune hyperthyroidism (NAH) is a rare type of autosomal dominant hyperthyroidism caused by constitutively active pathogenic variants of the thyrotropin receptor (TSHR) gene. Although affected family members present with varied levels of hyperthyroid features, even when the same pathogenic variant is present, total thyroidectomy followed by radioiodine therapy is recommended for long-term management. Herein, we present the case of an 18-year-old proband and her family members with NAH (TSHR-I640V), who presented with diverse thyroid dysfunctions: fluctuations between euthyroid and subclinical hyperthyroidism, mild hyperthyroidism, and overt hyperthyroidism. Almost all affected adult family members, except the proband, showed no progression of hyperthyroidism or thyroid enlargement. A family history of thyrotropin receptor antibodies (TRAb)-negative hyperthyroidism is important for the identification of NAH in adults before TSHR genetic testing can be performed. Ablative therapy is not necessary when familial NAH presents with late-onset mild hyperthyroidism without coexisting diseases.

Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

OBJECTIVES: Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis. METHODS: The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed. RESULTS: Case 1, a Hispanic male from Puerto Rico with hepatomegaly since age 2 months, was eventually diagnosed with PFIC3 following identification of a homozygous splice site variant in ATP binding cassette subfamily B member 4 (ABCB4) (c.2784-12T>C) at age 17 years by whole-exome sequencing (WES). Case 2 was a 37-year-old man with a history of alcoholism, abnormal liver function tests, and ductopenia on biopsy. Molecular testing revealed a pathogenic heterozygous ABCB4 mutation (c.1633C>T) variant leading to a diagnosis of PFIC3. Case 3 was a 2-year-old female initially presenting as a drug-induced liver injury but was diagnosed with PFIC10 following identification of a heterozygous frameshift mutation (p.Asp300Trpfs*19) and a heterozygous missense mutation (c.1357T>C) in myosin VB (MYO5B) by WES. CONCLUSIONS: These PFIC cases highlight the heterogenous presentation and diagnostic challenges, and they emphasize the role of next-generation sequencing, particularly the utility of WES.

[Neonatal epileptics syndromes]. / Síndromes epilépticos neonatales.

Neonatal epileptic syndromes are part of the genetic and metabolic epilepsies in this age group. Although they are not the most frequent cause of neonatal seizures, their early recognition allows for better diagnostic and therapeutic approaches. These syndromes can be classified into self-limited neonatal syndromes and early infantile epileptic and developmental encephalopathies (EIDEE). While they may share semiology in some types of seizures, such as sequential, and even share alterations in common genes in their etiology, their evolution is very different. In self-limited neonatal syndromes, seizures typically resolve within the first months of life with normal psychomotor development, giving rise to the term self-limited. However, the term benign should not be used as some may present recurrence of seizures, movement disorders, or learning disorders. In the case of EIDEE, seizures are usually refractory to treatment, affecting brain functions and neurodevelopment. In this review, our aim was to describe the electroclinical phenotype of neonatal epileptic syndromes, the most frequently involved genes and their clinical spectrum, their diagnostic approach, as well as the recommended treatments.

Los síndromes epilépticos neonatales hacen parte de las epilepsias de origen genético y metabólico en este grupo edad y aunque no son la causa más frecuente de crisis neonatales, su reconocimiento temprano permite dirigir mejor su enfoque diagnóstico y tratamiento. Pueden clasificarse en síndromes neonatales autolimitados y encefalopatías epilépticas y del desarrollo infantil temprano (EIDEE). Aunque pueden mostrar semiología similar en algunos tipos de crisis, como las secuenciales, e incluso comparten alteraciones en genes comunes en su etiología, su evolución es muy diferente. En los síndromes autolimitados, las crisis remiten en los primeros meses de vida alcanzando un desarrollo psicomotor normal, lo que da su nombre de autolimitado; sin embargo, el término benigno no debe utilizarse dado que algunos pueden presentar recurrencia de crisis, trastornos del movimiento o trastornos del aprendizaje. En las EIDEE las crisis suelen ser refractarias al tratamiento y se comprometen funciones cerebrales y el neurodesarrollo. En esta revisión describiremos el fenotipo electroclínico de los síndromes epilépticos neonatales, los genes más frecuentemente involucrados y su espectro clínico, su enfoque diagnóstico, así como los tratamientos recomendados.

Novel CTR9 germline pathogenic splice site variant in siblings with Wilms tumor from Tanzania.

Wilms tumor is the most common childhood renal malignancy. Though mostly non-genetic, it can be syndromic with the involvement of many Wilms tumor predisposing genes and non-syndromic with the involvement of four genes: WT1, REST, TRIM28, and CTR9. Familial and bilateral Wilms tumors do occur, but these are rare. So far, four Wilms tumor families with pathogenic variants in the CTR9 gene have been described, all (presumably) inherited from unaffected fathers, and three leading to deletion of exon 9. We are reporting female siblings, of whom one has a bilateral Wilms tumor, with a novel pathogenic splice site variant in the CTR9 gene, leading to deletion of exon 9, and inherited from their asymptomatic father. The loss of heterozygosity in the tumor was confirmed. In conclusion, CTR9 pathogenic variants are a very rare cause of Wilms tumors and typically result in familial Wilms tumors.

Synthesized economic evidence on the cost-effectiveness of screening familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a prevalent genetic disorder with global implications for severe cardiovascular diseases. Motivated by the growing recognition of the need for early diagnosis and treatment of FH to mitigate its severe consequences, alongside the gaps in understanding the economic implications and equity impacts of FH screening, this study aims to synthesize the economic evidence on the cost-effectiveness of FH screening and to analyze the impact of FH screening on health inequality. METHODS: We conducted a systematic review on the economic evaluations of FH screening and extracted information from the included studies using a pre-determined form for evidence synthesis. We synthesized the cost-effectiveness components involving the calculation of synthesized incremental cost-effectiveness ratios (ICERs) and net health benefit (NHB) of different FH screening strategies. Additionally, we applied an aggregate distributional cost-effectiveness analysis (DCEA) to assess the impact of FH screening on health inequality. RESULTS: Among the 19 studies included, over half utilized Markov models, and 84% concluded that FH screening was potentially cost-effective. Based on the synthesized evidence, cascade screening was likely to be cost-effective, with an ICER of $49,630 per quality-adjusted life year (QALY). The ICER for universal screening was $20,860 per QALY as per evidence synthesis. The aggregate DCEA for six eligible studies presented that the incremental equally distributed equivalent health (EDEH) exceeded the NHB. The difference between EDEH and NHB across the six studies were 325, 137, 556, 36, 50, and 31 QALYs, respectively, with an average positive difference of 189 QALYs. CONCLUSIONS: Our research offered valuable insights into the economic evaluations of FH screening strategies, highlighting significant heterogeneity in methods and outcomes across different contexts. Most studies indicated that FH screening is cost-effective and contributes to improving overall population health while potentially reducing health inequality. These findings offer implications that policies should promote the implementation of FH screening programs, particularly among younger population. Optimizing screening strategies based on economic evidence can help identify the most effective measures for improving health outcomes and maximizing cost-effectiveness.

Hepatocellular carcinoma associated with progressive intrahepatic familial cholestasis type 2: a case report.

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disorder typically presenting in infancy with cholestasis and rapidly progressing to cirrhosis. PFIC has been associated with an elevated risk of hepatocellular carcinoma (HCC), a neoplasm that is uncommon in children. PFIC type 4 has the strongest link to this type of cancer, although a few cases have also been connected to PFIC2. Herein, we report the case of a 2-year-old boy who underwent liver transplantation due to PFIC2. Histological examination showed cirrhosis and four small HCCs. Over a 20-year period following the transplantation, there was no recurrence of the disease or HCC. Although rare, HCC development can occur in PFIC and may complicate the prognosis. Liver transplantation offers a potential cure for both the metabolic disease and the neoplasm.