RESUMEN
Context: Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Objective: To determine whether reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to determine whether proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in determining low LDL levels in this condition. Design: We studied subjects from 19 families with ANGPTL3 mutations and subjects with familial combined hypobetalipoproteinemia type 1 (FHBL1) due to truncated apolipoprotein B (apoB) species. Results: First, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and HDL and LDL particle concentration correlated with plasma ANGPTL3 levels but only when the latter was <25% of normal (<60 ng/dL). Second, the very low-density lipoprotein particle concentration correlated strongly with plasma ANGPTL3 when the latter was <58% of normal. Third, both FHBL1 and FHBL2 subjects showed low levels of mature and LDL-bound PCSK9 and higher levels of its furin-cleaved form. Finally, LDL-bound PCSK9 is protected from cleavage by furin and binds to the LDL receptor more strongly than apoB-free PCSK9. Conclusions: Our results suggest that the hypolipidemic effects of ANGPTL3 mutations in FHBL2 are dependent on a threshold of plasma ANGPTL3 levels, with differential effects on various lipoprotein particles. The increased inactivation of PCSK9 by furin in FHBL1 and FHBL2 is likely to cause increased LDL clearance and suggests novel therapeutic avenues.
Asunto(s)
Angiopoyetinas/genética , Apolipoproteínas B/sangre , Predisposición Genética a la Enfermedad , Hipobetalipoproteinemias/genética , Adulto , Anciano , Proteína 3 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Western Blotting , Estudios de Cohortes , Femenino , Heterocigoto , Humanos , Hipobetalipoproteinemias/sangre , Hipobetalipoproteinemias/fisiopatología , Modelos Lineales , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Linaje , FenotipoRESUMEN
BACKGROUND AND AIMS: Fibrinogen gene mutations can rarely result in hepatic fibrinogen storage disease (HFSD). Herein, we report on the first Turkish family carrying the mutation p.Arg375Trp (fibrinogen Aguadilla) in the γ-chain of the fibrinogen (FGG) gene. METHODS: Clinical, laboratory and histopathological findings of the patient were documented. Molecular study of fibrinogen gene was performed in the patient and her family members. RESULTS: The proband was 5 years old girl presenting with advanced liver fibrosis of unknown origin. The child had very low plasma levels of fibrinogen and hypobetalipoproteinemia. Immunomorphologic and electron microscopic studies showed selective and exclusive accumulation of fibrinogen within the endoplasmic reticulum in liver biopsy of the patient. Patient, mother, two sisters and one brother carried p.Arg375Trp mutation (fibrinogen Aguadilla) in FGG gene. The patient was treated with ursodeoxycholic acid and carbamazepine. After 3 months, carbamazepine was suspended upon family decision and unresponsiveness of carbamazepine. CONCLUSIONS: HFSD is characterized by hypofibrinogenemia and accumulation of abnormal fibrinogen within hepatocytes. In addition, hypofibrinogenemia is associated with hypobetalipoproteinemia in Aguadilla mutation.
Asunto(s)
Afibrinogenemia , Carbamazepina/administración & dosificación , Fibrinógeno , Hipobetalipoproteinemias , Cirrosis Hepática , Ácido Ursodesoxicólico/administración & dosificación , Afibrinogenemia/diagnóstico , Afibrinogenemia/etiología , Afibrinogenemia/metabolismo , Preescolar , Colagogos y Coleréticos/administración & dosificación , Inductores del Citocromo P-450 CYP3A/administración & dosificación , Femenino , Fibrinógeno/análisis , Fibrinógeno/genética , Humanos , Hipobetalipoproteinemias/complicaciones , Hipobetalipoproteinemias/diagnóstico , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/fisiopatología , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cirrosis Hepática/fisiopatología , Mutación Missense , Resultado del TratamientoRESUMEN
Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are genetic diseases characterized by low density lipoprotein deficiency. ABL presents early in life with the gastroenterological manifestations of fat malabsorption, steatorrhea, and failure to thrive, and later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E. Heterozygous FHBL subjects are usually asymptomatic, but may develop fatty liver disease. In homozygous (compound heterozygous) FHBL, the clinical and biochemical features are indistinguishable from those of ABL and treatment recommendations are the same: dietary fat restriction to prevent steatorrhea, and long-term high-dose vitamin E and A supplementation to prevent or at least slow the progression of neuromuscular and retinal degenerative disease. Despite their low plasma vitamin E levels, individuals with heterozygous FHBL do not require vitamin E supplementation. There are conflicting reports on whether increased oxidative stress is seen in ABL; these differences may relate to the small size of patient groups as well as differences in patient age and dose of vitamin E supplementation, or the contribution from dietary sources of vitamin E. High density lipoproteins in ABL appear to be severely oxidized yet able to inhibit platelet aggregation by binding to scavenger receptor B1. We review the role of vitamin E and oxidative stress in ABL and FHBL.
Asunto(s)
Abetalipoproteinemia/fisiopatología , Hipobetalipoproteinemias/fisiopatología , Estrés Oxidativo , Vitamina E/uso terapéutico , Abetalipoproteinemia/tratamiento farmacológico , Heterocigoto , Homocigoto , Humanos , Hipobetalipoproteinemias/tratamiento farmacológico , Hipobetalipoproteinemias/genética , Vitamina E/sangreRESUMEN
OBJECTIVE: Angiopoietin-like 3 (Angptl3) is a regulator of lipoprotein metabolism at least by inhibiting lipoprotein lipase activity. Loss-of-function mutations in ANGPTL3 cause familial combined hypolipidemia through an unknown mechanism. APPROACH AND RESULTS: We compared lipolytic activities, lipoprotein composition, and other lipid-related enzyme/lipid transfer proteins in carriers of the S17X loss-of-function mutation in ANGPTL3 and in age- and sex-matched noncarrier controls. Gel filtration analysis revealed a severely disturbed lipoprotein profile and a reduction in size and triglyceride content of very low density lipoprotein in homozygotes as compared with heterozygotes and noncarriers. S17X homozygotes had significantly higher lipoprotein lipase activity and mass in postheparin plasma, whereas heterozygotes showed no difference in these parameters when compared with noncarriers. No changes in hepatic lipase, endothelial lipase, paraoxonase 1, phospholipid transfer protein, and cholesterol ester transfer protein activities were associated with the S17X mutation. Plasma free fatty acid, insulin, glucose, and homeostatic model assessment of insulin resistance were significantly lower in homozygous subjects compared with heterozygotes and noncarriers subjects. CONCLUSIONS: These results indicate that, although partial Angptl3 deficiency did not affect the activities of lipolytic enzymes, the complete absence of Angptl3 results in an increased lipoprotein lipase activity and mass and low circulating free fatty acid levels. This latter effect is probably because of decreased mobilization of free fatty acid from fat stores in human adipose tissue and may result in reduced hepatic very low density lipoprotein synthesis and secretion via attenuated hepatic free fatty acid supply. Altogether, Angptl3 may affect insulin sensitivity and play a role in modulating both lipid and glucose metabolism.
Asunto(s)
Angiopoyetinas/deficiencia , Ácidos Grasos no Esterificados/sangre , Hipobetalipoproteinemias/enzimología , Resistencia a la Insulina , Lipoproteína Lipasa/sangre , Adulto , Anciano , Análisis de Varianza , Proteína 3 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Angiopoyetinas/genética , Biomarcadores/sangre , Glucemia/análisis , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Regulación hacia Abajo , Femenino , Heterocigoto , Homocigoto , Humanos , Hipobetalipoproteinemias/sangre , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/fisiopatología , Insulina/sangre , Italia , Modelos Lineales , Lipasa/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Mutación , Triglicéridos/sangre , Regulación hacia ArribaRESUMEN
AIMS/HYPOTHESIS: Hepatic steatosis is strongly associated with hepatic and whole-body insulin resistance. It has proved difficult to determine whether hepatic steatosis itself is a direct cause of insulin resistance. In patients with familial hypobetalipoproteinaemia (FHBL), hepatic steatosis is a direct consequence of impaired hepatic VLDL excretion, independently of metabolic derangements. Thus, patients with FHBL provide a unique opportunity to investigate the relation between increased liver fat and insulin sensitivity. METHODS: We included seven male participants with FHBL and seven healthy matched controls. Intrahepatic triacylglycerol content and intramyocellular lipid content were measured using localised proton magnetic resonance spectroscopy (¹H-MRS). A two-step hyperinsulinaemic-euglycaemic clamp, using stable isotopes, was assessed to determine hepatic and peripheral insulin sensitivity. RESULTS: ¹H-MRS showed moderate to severe hepatic steatosis in patients with FHBL. Basal endogenous glucose production (EGP) and glucose levels did not differ between the two groups, whereas insulin levels tended to be higher in patients compared with controls. Insulin-mediated suppression of EGP during lower dose insulin infusion and insulin-mediated peripheral glucose uptake during higher dose insulin infusion were comparable between FHBL participants and controls. Baseline fatty acids and lipolysis (glycerol turnover) at baseline and during the clamp did not differ between groups. CONCLUSIONS/INTERPRETATION: In spite of moderate to severe hepatic steatosis, people with FHBL do not display a reduction in hepatic or peripheral insulin sensitivity compared with healthy matched controls. These results indicate that hepatic steatosis per se is not a causal factor leading to insulin resistance. TRIAL REGISTRATION: ISRCTN35161775.
Asunto(s)
Hígado Graso/fisiopatología , Hipobetalipoproteinemias/fisiopatología , Resistencia a la Insulina/fisiología , Adulto , Composición Corporal , Calorimetría Indirecta , Estudios de Casos y Controles , Técnica de Clampeo de la Glucosa , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Triglicéridos/metabolismo , Adulto JovenRESUMEN
Hypocholesterolemia is defined as total cholesterol (TC) and low density cholesterol (LDL-C) levels below the 5(th) percentile of the general population adjusted for age, gender and race. Hypocholesterolemia may be attributed to inherited disorders or several secondary causes. Inherited forms of hypocholesterolemia consist of a group of rare diseases. The best studied are familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). Clinical diagnosis rests on lipid levels and the pattern of inheritance after secondary causes are excluded. Patients with primary hypobetalipoproteinemias may manifest a variety of symptoms and signs affecting several organs (steatorrhea, neurological and ophalmological symptoms, non-alcoholic fatty liver disease) or be asymptomatic. Understanding hypocholesterolemia and the underlying molecular basis is of crucial importance since this may provide new insights in the treatment of hypercholesterolemia and cardiovascular disease.
Asunto(s)
Dislipidemias/etiología , Hipobetalipoproteinemias/etiología , Dislipidemias/diagnóstico , Dislipidemias/fisiopatología , Dislipidemias/terapia , Diagnóstico Precoz , Humanos , Hipobetalipoproteinemia Familiar por Apolipoproteína B/diagnóstico , Hipobetalipoproteinemia Familiar por Apolipoproteína B/genética , Hipobetalipoproteinemia Familiar por Apolipoproteína B/fisiopatología , Hipobetalipoproteinemia Familiar por Apolipoproteína B/terapia , Hipobetalipoproteinemias/diagnóstico , Hipobetalipoproteinemias/fisiopatología , Hipobetalipoproteinemias/terapia , Proproteína Convertasa 9 , Proproteína Convertasas , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismoRESUMEN
A 26-year-old male, the index patient, presented with persecutory delusions and suicidal behavior. He had 10 paternal male relatives in two prior generations. Five of them died by violent suicide and one, of the five, also committed a double homicide. The index patient was found to be hypocholesterolemic due to being heterozygous for a novel mutation of apolipoprotein B (apoB-29.4). His mother and paternal grandmother were normocholesterolemic, whereas a surviving paternal uncle was hypocholesterolemic and heterozygous for the apoB-29.4 mutation. This indicated that the index patient's father and paternal grandfather, both of which died by violent suicide, were obligate heterozygotes for the apoB-29.4 mutation and that the index patient inherited the mutation from his paternal grandfather. The odds ratio for the association between hypocholesterolemia and violent behavior in this family, where cholesterol status was known, was 16.9 (95% confidence interval 1.1-239.3). Therefore, our results support an inheritable relationship between violent behavior and hypocholesterolemia.
Asunto(s)
Agresión , Apolipoproteínas B/genética , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/fisiopatología , Mutación/genética , Adulto , Apolipoproteínas B/sangre , Western Blotting/métodos , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Humanos , Masculino , Oportunidad Relativa , Valores de ReferenciaRESUMEN
Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are inherited disorders of apolipoprotein B (apo B)-containing lipoproteins that result from mutations in apo B and microsomal triglyceride transfer protein (MTP) genes, respectively. Here we report three patients with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Two of them (probands F.A. and P.E.) had clinical and biochemical phenotype consistent with ABL. Proband F.A. was homozygous for a minute deletion/insertion (c.1228delCCCinsT) in exon 9 of MTP gene predicted to cause a truncated MTP protein of 412 amino acids. Proband P. E. was heterozygous for a mutation in intron 9 (IVS9-1G>A), previously reported in an ABL patient. We failed to find the second pathogenic mutation in MTP gene of this patient. No mutations were found in apo B gene. The third proband (D.F.) had a less severe lipoprotein phenotype which was similar to that of heterozygous FHBL and appeared to be inherited as a co-dominant trait. However, he had no mutations in apo B gene. He was found to be a compound heterozygote for two missense mutations (D384A and G661A), involving highly conserved regions of MTP. Since this proband was also homozygous for varepsilon2 allele of apolipoprotein E (apo E), it is likely that his hypobetalipoproteinemia derives from a combined effect of a mild MTP deficiency and homozygosity for apo E2 isoform.
Asunto(s)
Abetalipoproteinemia/genética , Proteínas Portadoras/genética , Hipobetalipoproteinemias/genética , Abetalipoproteinemia/fisiopatología , Adulto , Preescolar , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Hipobetalipoproteinemias/fisiopatología , Masculino , Linaje , FenotipoAsunto(s)
Quilomicrones/metabolismo , Hipobetalipoproteinemias , Animales , Apolipoproteína B-100 , Apolipoproteína B-48 , Apolipoproteínas B/sangre , Apolipoproteínas B/deficiencia , Diagnóstico Diferencial , Dieta con Restricción de Grasas , Humanos , Hipobetalipoproteinemias/etiología , Hipobetalipoproteinemias/fisiopatología , Pronóstico , Vitamina A/uso terapéutico , Vitamina E/uso terapéuticoRESUMEN
OBJECTIVE: To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia. METHODS: Brain and skeletal muscle bioenergetics were studied by in vivo phosphorus MR spectroscopy (31P-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindred with familial hypobetalipoproteinaemia. Plasma concentrations of vitamin E and coenzyme Q10 (CoQ10) were also assessed. RESULTS: Brain 31P-MRS disclosed in all patients a reduced phosphocreatine (PCr) concentration whereas the calculated ADP concentration was increased. Brain phosphorylation potential was reduced in the members by about 40%. Skeletal muscle was studied at rest in the three members and during aerobic exercise and recovery in the son and daughter. Only the mother showed an impaired mitochondrial function at rest. Both son and daughter showed an increased end exercise ADP concentration whereas the rates of postexercise recovery of PCr and ADP were slow in the daughter. The rate of inorganic phosphate recovery was reduced in both cases. Plasma concentration of vitamin E and CoQ10 was below the normal range in all members. CONCLUSIONS: Structural changes in mitochondrial membranes and deficit of vitamin E together with reduced availability of CoQ10 can be responsible for the multisystemic bioenergetic deficit. Present findings suggest that CoQ10 supplementation may be important in familial hypobetalipoproteinaemia.
Asunto(s)
Encéfalo/metabolismo , Encéfalo/fisiopatología , Metabolismo Energético , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/fisiopatología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fosfocreatina/metabolismo , Fosforilación , Mutación Puntual , Ubiquinona/sangre , Vitamina E/sangreRESUMEN
In a family in which the father was the mother's uncle, 3 of the 7 children were affected by a syndrome of malabsorption with various clinical symptoms. Diarrhea appeared in 2 of the children at birth, and in the third child at six months. The diarrhea led to failure-to-thrive, muscular wasting and abdominal swelling. However, the children improved spontaneously over the years. During childhood all 3 had manifest steatorrhea. Serum cholesterol was between 39 and 100 mg/dl, while triglycerides were normal to high. Reevaluation during the past year revealed areflexia, deficiency of vitamins A and E and of apoproteins A and B, and prolonged PT time in 2 of the children. Electron and light microscopy of small intestinal biopsies revealed vacuoles in the enterocytes. Electrophysiological tests revealed major disturbances in sensory conduction and brain-stem function. These cases differ from those described in the literature. Although in hypobetalipoproteinemia, 1 of the parents would be expected to be heterozygous and have low serum levels of APO B, in this family the parents had normal levels. Their children had low levels of serum APO A, while in patients with hypobetalipoproteinemia the levels are normal. There is a report of a case of deficiencies of both apolipoproteins, but the patient was asymptomatic, had chylomicronemia after a prolonged fast, and lower cholesterol levels than our patients. 8 other cases of apolipoprotein deficiency have been reported with biochemical characteristics similar to those of our patients, but with retention of chylomicrons in the small intestine.
Asunto(s)
Enfermedad Celíaca/genética , Hipobetalipoproteinemias/genética , Apoproteínas/sangre , Apoproteínas/deficiencia , Enfermedad Celíaca/etiología , Preescolar , Diarrea/etiología , Diarrea/fisiopatología , Insuficiencia de Crecimiento/etiología , Humanos , Hipobetalipoproteinemias/complicaciones , Hipobetalipoproteinemias/fisiopatología , Lactante , Recién Nacido , MasculinoRESUMEN
Serial somatosensory evoked potentials (SEPs) to median and posterior tibial nerve stimulation in a case with familial heterozygous hypobetalipoproteinemia and vitamin E deficiency were investigated over a period of 4 years. In serial SEPs to posterior tibial nerve stimulation, interpeak latencies between N20 and P2 were delayed even in the early clinical stage, although the peak latency of N20 was normal. N20 latency was delayed when the patient noted paresthesia of the lower extremities. Interpeak latencies between N20 and P2 were progressively prolonged, and finally both peaks disappeared. Progressive dysfunctions of spinal posterior columns and peripheral somatosensory pathways were discovered by serial SEP studies.
Asunto(s)
Ataxia Cerebelosa/etiología , Potenciales Evocados Somatosensoriales , Hipobetalipoproteinemias/fisiopatología , Enfermedades del Sistema Nervioso Periférico/etiología , Deficiencia de Vitamina E/fisiopatología , Ataxia Cerebelosa/fisiopatología , Humanos , Hipobetalipoproteinemias/sangre , Hipobetalipoproteinemias/complicaciones , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Nervio Tibial/fisiopatología , Vitamina E/uso terapéutico , Deficiencia de Vitamina E/complicacionesAsunto(s)
LDL-Colesterol/sangre , Hipobetalipoproteinemias/fisiopatología , Hipolipoproteinemias/fisiopatología , Complicaciones del Embarazo/fisiopatología , Adulto , Estradiol/sangre , Estriol/sangre , Femenino , Homocigoto , Humanos , Hipobetalipoproteinemias/sangre , Recién Nacido , Embarazo , Complicaciones del Embarazo/sangre , Progesterona/sangreRESUMEN
Progesterone synthesis by the human corpus luteum requires a source of cholesterol, which can be derived from both local synthesis and uptake of low density lipoproteins (LDL). When the corpus luteum is maintained in organ culture, progesterone synthesis is primarily dependent on LDL and the rate of progesterone production during growth in a LDL-free media is suboptimal. An in vivo situation analogous to that of corpus luteum grown in LDL-depleted media exists naturally in patients with abetalipoproteinemia. To determine whether a complete deficiency of plasma LDL affects serum concentrations of progesterone (particularly during the luteal phase) or those of other hormones, we have measured the serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, estrone, and progesterone during the menstrual cycle in a patient with phenotypic abetalipoproteinemia (on the basis of homozygous hypobetalipoproteinemia). Our results show a normal cyclical pattern with midcycle increases in the concentrations of luteinizing and follicle-stimulating hormones, prolactin, and estrogens but a distinctly subnormal increase in the luteal phase concentrations of progesterone. These results suggest that, in patients with phenotypic abetalipoproteinemia, the absence of LDL leads to an impairment in the maximal rates of production of progesterone by the corpus luteum.
Asunto(s)
Hipobetalipoproteinemias/fisiopatología , Hipolipoproteinemias/fisiopatología , Menstruación , Progesterona/sangre , Adulto , Cuerpo Lúteo/fisiopatología , Estradiol/sangre , Estrona/sangre , Femenino , Homocigoto , Humanos , Hipobetalipoproteinemias/genéticaRESUMEN
Corticosteroid synthesis in the human adrenal cortex requires a supply of cholesterol which can be derived from both local synthesis and the uptake of plasma lipoproteins. Studies with cultured adrenal cells have shown that such uptake is mediated through the interaction of plasma low density lipoproteins (LDL) and a specific cellular receptor (the LDL receptor). In the present study we have examined parameters of adrenal corticosteroid production in a patient with phenotypic abetalipoproteinemia (on the basis of homozygous hypobetalipoproteinemia) and in three of her relatives with inherently low levels of LDL (heterozygous hypobetalipoproteinemia). These studies sought to determine whether the absence of LDL or an inherent reduction in their plasma concentration results in alterations in corticosteroid production both under basal conditions and in response to prolonged stimulation with iv ACTH. Our results document normal parameters of corticosteroid production under basal conditions in both heterozygous and homozygous hypobetalipoproteinemia, but an impaired response to ACTH in the latter. This was manifested by significantly lower serum concentrations of cortisol as well as by reduced rates of excretion of 17OHCS, 17-ketosteroids, and urinary free cortisol during ACTH infusion. By inference, our results provide in vivo support for the view that plasma LDL serve as an important source of cholesterol for adrenal corticosteroid synthesis under conditions of sustained stimulation with ACTH.
Asunto(s)
Corticoesteroides/biosíntesis , Corteza Suprarrenal/fisiopatología , Hipobetalipoproteinemias/genética , Hipolipoproteinemias/genética , 17-Hidroxicorticoesteroides/orina , 17-Cetosteroides/orina , Adolescente , Adulto , Cosintropina , Femenino , Heterocigoto , Homocigoto , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Hipobetalipoproteinemias/fisiopatología , Cinética , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana EdadAsunto(s)
Hiperlipoproteinemias/fisiopatología , Hipolipoproteinemias/fisiopatología , Abetalipoproteinemia/fisiopatología , Humanos , Hiperlipoproteinemia Tipo I/fisiopatología , Hiperlipoproteinemia Tipo II/fisiopatología , Hiperlipoproteinemia Tipo III/fisiopatología , Hiperlipoproteinemia Tipo IV/fisiopatología , Hiperlipoproteinemia Tipo V/fisiopatología , Hiperlipoproteinemias/etiología , Hipobetalipoproteinemias/fisiopatología , Enfermedad de Tangier/fisiopatologíaRESUMEN
Acanthocytosis represents an unusually pathological variant of red cell morphology which is encountered in a diverse group of inherited and acquired disease states. While the morphological features are similar in all instances, the biochemical lesions frequently differ. Most demonstrable abnormalities involve lipids although those acanthocytes associated with the McLeod phenotype are probably due to an alteration in a membrane protein. Acanthocytes, regardless of their etiology, usually have a decreased survival in the circulation owing to splenic sequestration and destruction.