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Blood Jun 2023
Topics: Humans; Abetalipoproteinemia
PubMed: 37382999
DOI: 10.1182/blood.2023020260 -
JPGN Reports Nov 2022Cow's milk protein allergy (CMPA) is an abnormal immunologic response to bovine protein that can result in various gastrointestinal and cutaneous manifestations...
Cow's milk protein allergy (CMPA) is an abnormal immunologic response to bovine protein that can result in various gastrointestinal and cutaneous manifestations including diarrhea, failure to thrive, malabsorption, and even protein-losing enteropathy. We describe a case of a 7-month-old breastfed male who presented with severe atopic dermatitis, emesis, oily diarrhea, failure to thrive, electrolyte disturbance, and hemodynamic instability. Following stabilization, additional evaluation revealed concern for abetalipoproteinemia. Ultimately, the patient's symptoms resolved with introduction of an elemental formula and returned with reinitiation of cow's milk protein, confirming the diagnosis of severe CMPA. It is important for the general practitioner to be aware of the various presentations and have a high index of suspicion for CMPA as no symptom or diagnostic test is pathognomonic for diagnosis. Even though it can mimic other causes of malabsorption, a trial with extensively hydrolyzed or elemental formula should be attempted before undertaking invasive testing.
PubMed: 37168480
DOI: 10.1097/PG9.0000000000000246 -
Frontiers in Genetics 2022Dyslipidaemia represents a group of disorders of lipid metabolism, characterized by either an increase or decrease in lipid particles, usually associated with...
Dyslipidaemia represents a group of disorders of lipid metabolism, characterized by either an increase or decrease in lipid particles, usually associated with triglycerides, LDL cholesterol (LDL-C) and/or HDL cholesterol (HDL-C). Most hyperlipidaemias and HDL deficiencies confer an increased cardiovascular risk, while hypolipidaemia, such as abeta or hypobetalipoproteinemia, may present different manifestations ranging from poor weight progression to neurological manifestations. The aim of this study is to present 7 cases with rare dyslipidaemias associated with low LDL or low HDL cholesterol values, referred to our laboratory for the genetic identification of the cause of the dyslipidaemia. Lipid profile was determined for each individual in an automated equipment Integra Cobas (Roche). Molecular analysis was performed by NGS with a target panel of 57 genes involved in lipid metabolism (Sure select QXT, Agilent) and samples were run in a NextSEQ Sequencer (Illumina). Only genes associated to rare forms of low HDL-c or LDL-c were analysed for this work, namely: , , . All rare variants (MAF<5%) found in these genes were confirmed by Sanger sequencing. This study includes 7 index cases (IC), with the following clinical diagnoses: Fish Eye Disease (1), Hypoalphalipoproteinemia (1) and Abetalipoproteinemia (ABL) / Familial Hypobetalipoproteinemia (FHBL) (5). We have identified one IC with a compound heterozygosity in causing Fish Eye Disease and one IC with a variant in in homozygosity causing Tangier disease. We found variants causing homozygous FHBL in 2 IC, one of whom has an undescribed pathogenic variant in homozygosity in (c.12087+1G>A) and the other is a possible compound heterozygous for variants c.2604+1G>A and c.4651C>T/p.(Gln1551*). In two patients only a variant in heterozygosity (c.3365delG/p.(Gly1122Vfs*62) and c.11095A>T/p.(Arg3699*)). In the remaining patient, no variants were identified. NGS proved to be a fundamental key for genetic testing of rare lipid disorders, allowing us to find the genetic cause of disease in 6/7 patients with low HDL-c and LDL-c. Patients with these rare conditions should be identified as early as possible in order to minimize or prevent clinical manifestations. The unsolved case is still under investigation.
PubMed: 37138899
DOI: 10.3389/fgene.2022.1088040 -
Expert Review of Endocrinology &... May 2023Hypocholesterolemia results from genetic - both monogenic and polygenic - and non-genetic causes and can sometimes be a source of clinical concern. We review etiologies... (Review)
Review
INTRODUCTION
Hypocholesterolemia results from genetic - both monogenic and polygenic - and non-genetic causes and can sometimes be a source of clinical concern. We review etiologies and sequelae of hypocholesterolemia and therapeutics inspired from genetic hypocholesterolemia.
AREAS COVERED
Monogenic hypocholesterolemia disorders caused by the complete absence of apolipoprotein (apo) B-containing lipoproteins (abetalipoproteinemia and homozygous hypobetalipoproteinemia) or an isolated absence of apo B-48 lipoproteinemia (chylomicron retention disease) lead to clinical sequelae. These include gastrointestinal disturbances and severe vitamin deficiencies that affect multiple body systems, i.e. neurological, musculoskeletal, ophthalmological, and hematological. Monogenic hypocholesterolemia disorders with reduced but not absent levels of apo B lipoproteins have a milder clinical presentation and patients are protected against atherosclerotic cardiovascular disease. Patients with heterozygous hypobetalipoproteinemia have somewhat increased risk of hepatic disease, while patients with PCSK9 deficiency, ANGPTL3 deficiency, and polygenic hypocholesterolemia typically have anunremarkable clinical presentation.
EXPERT OPINION
In patients with severe monogenic hypocholesterolemia, early initiation of high-dose vitamin therapy and a low-fat diet are essential for optimal prognosis. The molecular basis of monogenic hypocholesterolemia has inspired novel therapeutics to help patients with the opposite phenotype - i.e. elevated apo B-containing lipoproteins. In particular, inhibitors of PCSK9 and ANGPTL3 show important clinical impact.
Topics: Humans; Proprotein Convertase 9; Hypobetalipoproteinemias; Apolipoproteins B; Lipoproteins; Cholesterol; Angiopoietin-Like Protein 3
PubMed: 37089071
DOI: 10.1080/17446651.2023.2204932 -
Movement Disorders Clinical Practice Mar 2023
PubMed: 36949797
DOI: 10.1002/mdc3.13626 -
Journal of Ayub Medical College,... 2023Klipple-Trenaunay syndrome (KTS) is an extremely rare congenital vascular disorder with poorly defined incidence and prevalence. We report a case of a patient who...
Klipple-Trenaunay syndrome (KTS) is an extremely rare congenital vascular disorder with poorly defined incidence and prevalence. We report a case of a patient who presented after road traffic accident with primary complaints of poor wound healing and persistent bleeding from wound site. Discernible presence of arteriovenous malformation and skin hypertrophy since birth lead to the diagnosis of Klipple-Trenaunay syndrome (KTS). There was an incidental finding of acanthocytosis on peripheral film of blood which remained elevated even after clinical improvement of the patient. This case report highlights a close association of marked acanthocytosis of red blood cells and Klipple-Trenaunay syndrome.
Topics: Humans; Abetalipoproteinemia; Erythrocytes
PubMed: 36849406
DOI: 10.55519/JAMC-01-11307 -
Nutrients Jan 2023Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in and genes,...
Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in and genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (-57.0 ± 2.6% to -83.9 ± 1.6%) and cholesterol (-35.3 ± 4.4% to -60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (-41.5 ± 3.7% to -97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). silencing led to a more severe phenotype than silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.
Topics: Humans; alpha-Tocopherol; Apolipoproteins B; Caco-2 Cells; Enterocytes; Hypobetalipoproteinemias; Monomeric GTP-Binding Proteins; Vitamin E
PubMed: 36771214
DOI: 10.3390/nu15030505 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jan 2023To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. The... (Review)
Review
To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. The clinical, laboratory, genetic, and liver histology data of a boy with Ho-FHBL managed in the hepatology ward of the Children's Hospital of Fudan University in May 2021 were retrospectively analyzed. The literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to May 2022) with "familial hypobetalipoproteinemia" or "hypobetalipoproteinemias" or "hypo beta lipoproteinemia" or "hypolipoproteinemias" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of Ho-FHBL caused by APOB gene variations. The male patient was admitted to the hospital due to abnormal liver function tests for 8 months at the age of 4 years and 6 months. Blood biochemistry showed transaminitis and abnormally low serum levels of lipids. Liver biopsy revealed fatty liver with inflammation and early cirrhosis (Brunt score was F3G2S4). Whole exome sequencing revealed two novel variants of APOB gene (c.3745C>T, p.Q1249 * from the father and c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT, p.T1530Kfs * 12 from the mother). He was diagnosed as Ho-FHBL caused by APOB gene compound heterozygous variations. Literature search retrieved 36 English literatures and 0 Chinese literature. A total of 55 (23 males and 32 females) Ho-FHBL cases, including this one, were caused by 54 APOB gene pathogenic variants (23 frameshift, 15 nonsense, 7 missense, 8 splice and 1 gross deletions). The age of the last follow-up was between 1 month and 75 years. Among them, 28 cases had lipid malabsorption, 19 cases had early dysplasia, 12 cases had no symptoms. Twenty-one patients had symptoms related to fat soluble vitamin deficiency, including 14 cases of acanthocytosis, 10 cases of neurological symptoms, and 6 cases of ocular lesions. Thirty-four patients had liver involvement, including 25 cases of elevated transaminase, 21 cases of fatty liver, 15 cases of hepatomegaly, 9 cases of liver fibrosis, 3 cases of liver cirrhosis, 1 case of hepatic hemangioma and 1 case of liver neoplastic nodule. The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. Patients may have lipid malabsorption and (or) early dysplasia, or symptom-free. Liver involvement is common.
Topics: Child; Female; Humans; Male; Child, Preschool; Infant; Abetalipoproteinemia; Retrospective Studies; Hypobetalipoproteinemias; Fatty Liver; Apolipoproteins B; Lipids
PubMed: 36594125
DOI: 10.3760/cma.j.cn112140-20220926-00838