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- Familial and Multifactorial Chylomicronemia Syndrome: Insights from Clinically Diagnosed Cases in PortugalPublication . Alves, Ana Catarina; Ferreira, Maria; Ferreira, Ana Cristina; Padeira, Gonçalo; Gaspar, Ana; Duarte, João Sequeira; Rato, Quitéria; Gonçalves, Filipa Sousa; Aguiar, Patrício; Cruz, Diogo; Bourbon, MafaldaFamilial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in one of five canonical genes, LPL, APOC2, GPIHBP1, APOA5, and LMF1. These variants result in impaired hydrolysis of triglyceride-rich lipoproteins, leading to clinical features such as xanthomas, abdominal pain, hepatomegaly, hepatosplenomegaly, lipemia retinalis, and recurrent pancreatitis. In contrast, Multifactorial Chylomicronemia Syndrome (MCS) often involves monoallelic variants in these genes and/or a high polygenic risk score, contributing to the severe hypertriglyceridemia phenotype. Clinically, FCS and MCS have a similar presentation, requiring genetic analysis for differentiation. This study aimed to clinically and molecularly characterize 42 individuals with severe hypertriglyceridemia in Portugal. Biochemical lipid profile and molecular analysis of the five canonical genes were performed. Moulin's score was applied to 14 cases; for the remaining cases, all data could not be obtained. The average pre-treatment triglyceride level was 2570 mg/dL. Fourteen individuals had pancreatitis, four had hepatomegaly, and three presented with both conditions. Eight cases have biallelic variants: five in LPL (three with identical variants, two with different variants), one in APOC2, one frameshift variant in LMF1 and one total exon 4 deletion in GPIHBP1 (all with identical variants). For these cases, the Moulin score obtained was FCS very likely. Twenty cases have heterozygous variants in LPL, APOA5, LMF1, and GPIHBP1 and were classified as MCS. For one of these cases, the Moulin score was FCS very likely. Ten patients have a negative genetic study, 5 of which had a score of unlikely FCS. Four are still under study. Early identification of FCS is critical to prevent or mitigate its severe complications. A confirmed molecular diagnosis enables accurate differentiation between FCS and MCS, leading to improved clinical management and prognosis. This study underscores the importance of integrating genetic analysis into the diagnostic workup of severe hypertriglyceridemia.
- Familial Chylomicronemia Syndrome: Clinical and Molecular Data From a Portuguese CohortPublication . Alves, Ana Catarina; Ferreira, Maria; Ferreira, Ana Cristina; Padeira, Gonçalo; Gaspar, Ana; Duarte, João Sequeira; Rato, Quitéria; Gonçalves, Filipa Sousa; Aguiar, Patrício; Cruz, Diogo; Raimundo, Anabela; Bourbon, MafaldaFamilial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder caused by biallelic variants in LPL, APOC2, GPIHBP1, APOA5, or LMF1. These defects impair triglyceride-rich lipoprotein hydrolysis, leading to xanthomas, abdominal pain, hepatomegaly, lipemia retinalis, and recurrent pancreatitis. Multifactorial Chylomicronemia Syndrome (MCS) often results from monoallelic variants in these genes and/or a high polygenic risk score, presenting a similar phenotype; thus, genetic testing is required for accurate differentiation. This study aimed to clinically and genetically characterize 45 individuals with severe hypertriglyceridemia in Portugal. Lipid profile and molecular analysis of the five canonical genes were performed. Moulin’s score was applied in 17 cases. The mean pretreatment triglyceride level was 2570 mg/dL. Sixteen individuals had pancreatitis, four had hepatomegaly, and three both conditions. Ten cases carried biallelic variants: five in LPL (three identical, two compound heterozygous), one in APOC2, one frameshift in LMF1, one frameshift and one stop in APOA5, and one total exon 4 deletion in GPIHBP1 (all identical variants). All were classified as “very likely FCS” by Moulin’s score. Twenty-one individuals had heterozygous variants in LPL, APOA5, LMF1, and GPIHBP1 and were considered MCS; three of them also scored as “very likely FCS.” Ten patients had negative genetic studies (five scored as “unlikely FCS”), and four remain under investigation. Early recognition of FCS is crucial to prevent life-threatening complications. A confirmed molecular diagnosis enables precise distinction between FCS and MCS, improving management and prognosis. These findings underscore the importance of incorporating genetic testing into the diagnostic workup of severe hypertriglyceridemia in Portugal.
- Familial Partial Lipodystrophy, Dunnigan- type: 2 families identified in a genetic laboratoryPublication . Alves, Ana Catarina; Medeiros, Ana Margarida; Ferreira, Maria; Miranda, Beatriz; Moldavan, Oana; Travessa, André; Rodrigues, Márcia; Bourbon, MafaldaLipodystrophies are a clinically heterogeneous group of acquired or inherited disorders affecting adipose tissue distribution. familial partial lipodystrophy, Dunnigan-type (FPLD2, OMIM 151660) is the most prevalent subtype and is an autosomal dominant disease characterized by the selective absence of adipose tissue in the extremities and trunk, with fat accumulation in the face, neck, and supraclavicular region. Individuals exhibit a muscular, hypertrophic appearance, particularly in the lower limbs. Affected individuals are born with a normal fat distribution but may present hyperlipidemia in childhood and begin to progressively lose subcutaneous fat after puberty. Later in life, they frequently develop metabolic complications, including hypertriglyceridemia, insulin resistance, diabetes mellitus, hepatic steatosis, and hypertension. In women, acanthosis nigricans, hirsutism, menstrual irregularities, and polycystic ovarian disease are commonly observed. Notably, the phenotype appears more pronounced in females, potentially leading to underdiagnosis in males due to lighter physical changes. Approximately 75% of patients with a clinical diagnosis of FPLD2 reported in the literature carry the same LMNA variant, p.(Arg482Trp) in exon 6 of the Lamina gene (LMNA) The aim of this study was to clinically and molecularly characterize two Portuguese families with a clinical diagnosis of lipodystrophy. We present the clinical and genetic characterization of two kindreds with multiple affected family members of different ages. Sequencing of the LMNA gene was performed by PCR and direct sequencing of all exons. Both index cases were found to carry the most common LMNA variant in heterozygosity p.(Arg482Trp), a missense variant in exon 6. Family screening identified six additional heterozygous carriers in Family I (including two children) and four in Family II (including one children). Both index cases were women and exhibited the characteristic of FPLD2 phenotype. Given the high prevalence of premature and severe cardiovascular events in these patients, early diagnosis is crucial for implementing appropriate treatment strategies and preventing disease progression. The genetic diagnosis allows for an earlier diagnosis, granting a better clinical counselling regarding lifestyle modifications since adolescence and a personalized treatment plan to reduce their risk of coronary heart disease (CHD).
- Role of 13C-urea breath test in experimental model of Helicobacter pylori infection in micePublication . Santos, António Mário; Lopes, Teresa; Oleastro, Mónica; Chaves, Paula; Cordeiro, Rita; Ferreira, Maria; Pereira, Teresa; Machado, Jorge; Guerreiro, António SousaBACKGROUND: Animal models have been widely used to study Helicobacter pylori infection. Evaluation of H. pylori infection status following experimental inoculation of mice usually requires euthanasia. The (13) C-urea breath test ((13) C-UBT) is both sensitive and specific for detection of H. pylori in humans. Thus, it would be very useful to have such a test with the same accuracy for the follow-up of this infection in animal models of gastric infection. Accordingly, the purpose of this study was to develop and evaluate a (13) C-UBT method for following the course of H. pylori infection in a mouse model. MATERIAL AND METHODS: A total of 50 female C57BL/6 mice were gavaged three times with either 10(8) colony-forming units of H. pylori (n=29) or saline solution only (n=21). After 2 months of infection, mice were fasted for 14 hours and (13) C-UBT was performed using 300 μg of (13) C-urea. The mice were killed, and the stomach was removed and processed for immunohistochemistry and PCR. RESULTS: The optimal time for breath sample collection in mice was found to be 15 minutes. The (13) C-UBT cutoff was set at 3.0‰ δPDB. Using PCR as the gold standard, the sensitivity of (13) C-UBT and immunohistochemistry was 96.6 and 72.4%, respectively, while the specificity was 85.7 and 95.2%, respectively. CONCLUSIONS: (13) C-UBT was shown to be a reliable method for the detection of H. pylori infection in C57BL/6 mice and was even more accurate than immunohistochemistry. The use of (13) C-UBT in the mouse model of H. pylori infection can be very useful to detect the bacterium without the need to kill the animals in long-term time course studies.