-
Zhonghua Er Ke Za Zhi = Chinese Journal... Oct 2022
Topics: Abetalipoproteinemia; Cilia; Humans; Kartagener Syndrome
PubMed: 36207861
DOI: 10.3760/cma.j.cn112140-20220614-00548 -
Hepatology (Baltimore, Md.) Oct 2019The mechanisms by which alterations in intestinal bile acid (BA) metabolism improve systemic glucose tolerance and hepatic metabolic homeostasis are incompletely...
The mechanisms by which alterations in intestinal bile acid (BA) metabolism improve systemic glucose tolerance and hepatic metabolic homeostasis are incompletely understood. We examined metabolic adaptations in mice with conditional intestinal deletion of the abetalipoproteinemia (ABL) gene microsomal triglyceride transfer protein (Mttp-IKO), which blocks chylomicron assembly and impairs intestinal lipid transport. Mttp-IKO mice exhibit improved hepatic glucose metabolism and augmented insulin signaling, without weight loss. These adaptations included decreased BA excretion, increased pool size, altered BA composition, and increased fibroblast growth factor 15 production. Mttp-IKO mice absorb fructose normally but are protected against dietary fructose-induced hepatic steatosis, without weight loss or changes in energy expenditure. In addition, Mttp-IKO mice exhibit altered cecal microbial communities, both at baseline and following fructose feeding, including increased abundance of Bacteroides and Lactobacillus genera. Transplantation of cecal microbiota from chow-fed Mttp-IKO mice into antibiotic-treated wild-type recipients conferred transmissible protection against fructose-induced hepatic steatosis in association with a bloom in Akkermansia and increased Clostridium XIVa genera, whose abundance was positively correlated with fecal coprostanol and total neutral sterol excretion in recipient mice. However, antibiotic-treated Mttp-IKO mice were still protected against fructose-induced hepatic steatosis, suggesting that changes in microbiota are not required for this phenotype. Nevertheless, we found increased abundance of fecal Akkermansia from two adult ABL subjects with MTTP mutations compared to their heterozygous parents and within the range noted in six healthy control subjects. Furthermore, Akkermansia abundance across all subjects was positively correlated with fecal coprostanol excretion. Conclusion: The findings collectively suggest multiple adaptive pathways of metabolic regulation following blocked chylomicron assembly, including shifts in BA signaling and altered microbial composition that confer a transmissible phenotype.
Topics: Adaptation, Physiological; Akkermansia; Animals; Bile Acids and Salts; Biological Transport; Carrier Proteins; Chylomicrons; Disease Models, Animal; Fatty Liver; Fructose; Gastrointestinal Microbiome; Glucose Tolerance Test; Humans; Intestinal Mucosa; Lipid Metabolism; Mice; Mice, Inbred C57BL; Random Allocation; Sensitivity and Specificity; Signal Transduction; Verrucomicrobia
PubMed: 31004524
DOI: 10.1002/hep.30669 -
Journal of Clinical Immunology Jul 2020X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the CYBB gene (located on Xp21.1). Patients with large deletions on...
BACKGROUND
X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the CYBB gene (located on Xp21.1). Patients with large deletions on chromosome Xp21.1 can present with the McLeod phenotype and also Duchenne muscular dystrophy or retinitis pigmentosa. The objective of the present study was to describe a series of French patients with CGD and the McLeod phenotype.
METHODS
We retrospectively collected data from the medical records of 8 patients with CGD and the McLeod phenotype registered at the French National Reference Center for blood types.
RESULTS
The median age at diagnosis of CGD was 1.2 years, the median age at diagnosis of the McLeod phenotype was 4.5 years, and the median length of follow-up was 15.2 years. Four patients displayed allo-immunization, with anti-KEL20 and anti-XK1 (formerly known as anti-KL) antibodies. Five of the 6 patients with available blood smears had acanthocytosis. Neuropsychiatric, muscle-related, and ocular manifestations were present in 4, 2, and 1 of the patients, respectively. Three of the 4 patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT) are alive. Overall, 5 patients are alive, and 3 are alive and well.
CONCLUSION
This is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients.
Topics: Abetalipoproteinemia; Adolescent; Adult; Child; Child, Preschool; Female; Follow-Up Studies; France; Granulomatous Disease, Chronic; Humans; Infant; Isoantibodies; Male; NADPH Oxidase 2; Neuroacanthocytosis; Retrospective Studies; Survival Analysis; Young Adult
PubMed: 32562208
DOI: 10.1007/s10875-020-00791-w -
Journal of Clinical Lipidology Apr 2024Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (MTTP) gene. This...
Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (MTTP) gene. This disease is characterized by a deficiency in the secretion of apolipoprotein B-containing lipoproteins. Patients with ABL present with neurological, hematological, and gastrointestinal symptoms due to fat malabsorption and a deficiency in liposoluble vitamins. In this report, we present a total of four ABL cases, including three new cases, all originating from the same French-Canadian founder population in Saguenay-Lac-Saint-Jean, Québec, Canada. These individuals are homozygous for the same pathogenic variant in the MTTP gene (c.419dup, p.Asn140Lysfs*2). We found that this variant is more common than anticipated in this population, with an estimated carrier frequency of 1:203. Early diagnosis is essential to initiate treatment known to prevent complications associated with ABL. Population carrier screening or newborn screening for ABL should be considered in this French-Canadian founder population.
PubMed: 38908974
DOI: 10.1016/j.jacl.2024.04.132 -
The Journal of Infectious Diseases Jul 2019Antimicrobial resistance in Neisseria gonorrhoeae is a major issue of public health, and there is a critical need for the development of new antigonococcal strategies....
Antimicrobial resistance in Neisseria gonorrhoeae is a major issue of public health, and there is a critical need for the development of new antigonococcal strategies. In this study, we investigated the effectiveness of antimicrobial blue light (aBL; wavelength, 405 nm), an innovative nonpharmacological approach, for the inactivation of N. gonorrhoeae. Our findings indicated that aBL preferentially inactivated N. gonorrhoeae, including antibiotic-resistant strains, over human vaginal epithelial cells in vitro. Furthermore, no aBL-induced genotoxicity to the vaginal epithelial cells was observed at the radiant exposure used to inactivate N. gonorrhoeae. aBL also effectively inactivated N. gonorrhoeae that had attached to and invaded into the vaginal epithelial cells in their cocultures. No gonococcal resistance to aBL developed after 15 successive cycles of inactivation induced by subtherapeutic exposure to aBL. Endogenous aBL-activatable photosensitizing porphyrins in N. gonorrhoeae were identified and quantified using ultraperformance liquid chromatography, with coproporphyrin being the most abundant species in all N. gonorrhoeae strains studied. Singlet oxygen was involved in aBL inactivation of N. gonorrhoeae. Together, these findings show that aBL represents a potential potent treatment for antibiotic-resistant gonococcal infection.
Topics: Abetalipoproteinemia; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Epithelial Cells; Female; Gonorrhea; Humans; Light; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Oxygen; Sodium Azide; Vagina
PubMed: 30629196
DOI: 10.1093/infdis/jiz018 -
Journal of Pediatric Hematology/oncology Apr 2021We report a probable case of abetalipoproteinemia in an infant who presented with unusual symptoms of late-onset vitamin K deficiency. Abetalipoproteinemia is a rare...
We report a probable case of abetalipoproteinemia in an infant who presented with unusual symptoms of late-onset vitamin K deficiency. Abetalipoproteinemia is a rare autosomal recessive disease caused by mutation of the microsomal triglyceride transfer protein gene, resulting in the absence of microsomal triglyceride transfer protein function in the small bowel. It is characterized by the absence of plasma apolipoprotein B-containing lipoproteins, fat malabsorption, hypocholesterolemia, retinitis pigmentosa, progressive neuropathy, myopathy, and acanthocytosis. A biopsy of the small intestine characteristically shows marked lipid accumulation in the villi of enterocytes. Large supplements of fat-soluble vitamins A, D, E, and K have been shown to limit neurologic and ocular manifestations. Dietary fat intake is limited to medium-chain triglycerides.
Topics: Abetalipoproteinemia; Duodenum; Enterocytes; Female; Humans; Infant; Infant, Newborn; Vitamin K Deficiency
PubMed: 32433446
DOI: 10.1097/MPH.0000000000001831 -
Journal of Clinical Lipidology 2024Familial hypobetalipoproteinemias (FHBL) are rare genetic diseases characterized by lipid malabsorption. We focused on abetalipoproteinemia (FHBL-SD1) and chylomicron...
BACKGROUND
Familial hypobetalipoproteinemias (FHBL) are rare genetic diseases characterized by lipid malabsorption. We focused on abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3), caused by mutations in microsomal triglyceride transfer protein (MTTP) and SAR1B genes, respectively. Treatments include a low-fat diet and high-dose fat-soluble vitamin supplementations. However, patients are not supplemented in carotenoids, a group of lipid-soluble pigments essential for eye health.
OBJECTIVE
Our aim was to evaluate carotenoid absorption and status in the context of hypobetalipoproteinemia.
METHODS
We first used knock-out Caco-2/TC7 cell models of FHBL-SD1 and FHBL-SD3 to evaluate carotenoid absorption. We then characterized FHBL-SD1 and FHBL-SD3 patient status in the main dietary carotenoids and compared it to that of control subjects.
RESULTS
In vitro results showed a significant decrease in basolateral secretion of α- and β-carotene, lutein, and zeaxanthin (-88.8 ± 2.2 % to -95.3 ± 5.8 %, -79.2 ± 4.4 % to -96.1 ± 2.6 %, -91.0 ± 4.5 % to -96.7 ± 0.3 % and -65.4 ± 3.6 % to -96.6 ± 1.9 %, respectively). Carotenoids plasma levels in patients confirmed significant deficiencies, with decreases ranging from -89 % for zeaxanthin to -98 % for α-carotene, compared to control subjects.
CONCLUSION
Given the continuous loss in visual function despite fat-soluble vitamin treatment in some patients, carotenoid supplementation may be of clinical utility. Future studies should assess the correlation between carotenoid status and visual function in aging patients and investigate whether carotenoid supplementation could prevent their visual impairment.
Topics: Humans; Caco-2 Cells; Zeaxanthins; Hypobetalipoproteinemias; Carotenoids; Vitamins; Lipids; Monomeric GTP-Binding Proteins; Syndactyly
PubMed: 37989694
DOI: 10.1016/j.jacl.2023.10.010 -
Movement Disorders Clinical Practice Mar 2023
PubMed: 36949797
DOI: 10.1002/mdc3.13626 -
Journal of Clinical Research in... Nov 2020Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results...
Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and TG levels according to her age. The peripheral blood smear revealed acanthocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of ABL and central hypothyroidism has not previously been reported. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the gene.
Topics: Abetalipoproteinemia; Carrier Proteins; Female; Humans; Hypothyroidism; Infant; Mutation; Prognosis
PubMed: 31914726
DOI: 10.4274/jcrpe.galenos.2019.2019.0144 -
Gastroenterology Nov 2020
Topics: Abetalipoproteinemia; Biopsy; Child, Preschool; Duodenum; Endoscopy, Digestive System; Humans; Intestinal Mucosa; Male; Steatorrhea
PubMed: 32311359
DOI: 10.1053/j.gastro.2020.03.079