RESUMEN
INTRODUCTION: Hereditary pyropoikilocytosis (HPP) is a heterogeneous inherited disorder of red blood cell (RBC) membrane and cytoskeletal proteins that leads to hemolytic anemia. HPP is characterized by marked poikilocytosis, microspherocytes, RBC fragmentation, and elliptocytes on peripheral blood smear. Mutations in SPTA1 can cause HPP due to a quantitative defect in α-spectrin and can lead to profound fetal anemia and nonimmune hydrops fetalis, which can be managed with intrauterine transfusion. CASE PRESENTATION: We present a case of a 26-year-old G4P2102 woman of Amish-Mennonite ancestry with a pregnancy complicated by fetal homozygosity for an SPTA1 gene variant (SPTA1c.6154delG) as well as severe fetal anemia and hydrops fetalis, which was managed with four intrauterine transfusions between 26 and 30 weeks gestation. Pre-transfusion peripheral smears from fetal blood samples showed RBC morphology consistent with HPP. The neonate had severe hyperbilirubinemia at birth, which has resolved, but remains transfusion-dependent at 6 months of life. DISCUSSION/CONCLUSION: To our knowledge, this is the first report that correlates homozygosity of the SPTA1c.6154delG gene variant with RBC dysmorphology and establishes the diagnosis of HPP.
Asunto(s)
Anemia Hemolítica , Eliptocitosis Hereditaria , Enfermedades Fetales , Enfermedades Hematológicas , Embarazo , Femenino , Recién Nacido , Humanos , Adulto , Hidropesía Fetal/diagnóstico , Hidropesía Fetal/genética , Hidropesía Fetal/terapia , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/diagnóstico , Eliptocitosis Hereditaria/genética , Proteínas del Citoesqueleto , Anemia Hemolítica/complicacionesRESUMEN
Nineteen reports of 41 cases of acquired red cell elliptocytosis associated with a chronic myeloid neoplasm are described. Although the majority of cases have an abnormality of the long arm of chromosome 20, del(q20), several cases do not. Moreover, in one case a specific qualitative abnormality of red cell protein band 4.1(4.1R) was reported; however, several subsequent cases could find no abnormality of a red cell membrane protein or found a different abnormality, usually quantitative. Thus, this striking red cell phenotypic feature, acquired elliptocytosis, seen in myelodysplastic syndrome and other chronic myeloproliferative diseases, closely simulating the red cell phenotype of hereditary elliptocytosis, has an unexplained genetic basis, presumably as the result of an acquired mutation(s) in some chronic myeloid neoplasms.
Asunto(s)
Eliptocitosis Hereditaria , Trastornos Mieloproliferativos , Neoplasias , Humanos , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/genética , Proteínas de la Membrana/genética , Neoplasias/metabolismo , Eritrocitos/metabolismo , Membrana Eritrocítica/metabolismo , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/metabolismo , Proteínas del Citoesqueleto/genéticaAsunto(s)
Eliptocitosis Hereditaria/genética , Mutación del Sistema de Lectura , Mutación Puntual , Espectrina/genética , Globinas beta/genética , Anemia Hipocrómica/genética , Células Cultivadas , Niño , Eliptocitosis Hereditaria/complicaciones , Exones/genética , Femenino , Estudios de Asociación Genética , Heterocigoto , Humanos , Ictericia/etiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/complicaciones , Conformación Proteica , Rasgo Drepanocítico/genéticaRESUMEN
Hereditary pyropoikilocytosis is a subtype of hereditary elliptocytosis because of biallelic mutations of SPTA1, SPTB, and EPB41. The authors present a proband with neonatal jaundice and hemolytic anemia, with poikilocytosis in the blood film. Targeted next-generation sequencing identified Q267del trans to the αLELY allele in SPTA1. In addition, the proband presented coexisting Gilbert syndrome as determined by homozygous mutation of UGT1A1. Investigation of 13 relatives and his sibling revealed that only his sibling showed the same phenotype and genotype as the proband. This is the first report of molecular confirmation of coexisting hereditary pyropoikilocytosis and Gilbert syndrome and a novel mutation in SPTA1.
Asunto(s)
Anemia Hemolítica/patología , Eliptocitosis Hereditaria/complicaciones , Enfermedad de Gilbert/complicaciones , Ictericia Neonatal/patología , Mutación , Espectrina/genética , Anemia Hemolítica/etiología , Preescolar , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Ictericia Neonatal/etiología , Masculino , Linaje , Fenotipo , PronósticoAsunto(s)
Eliptocitosis Hereditaria/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Médula Ósea/patología , Preescolar , Eliptocitosis Hereditaria/diagnóstico , Eritrocitos Anormales/patología , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnósticoRESUMEN
Objectives: Hereditary elliptocytosis (HE) is inherited in an autosomal dominant fashion, and the majority of HE-associated defects occur due to qualitative and quantitative defects in the RBC membrane skeleton proteins α-spectrin, ß-spectrin, or protein 4.1R. The complex EPB41 gene encodes a diverse family of protein 4.1R isoforms which are key components of the erythroid membrane skeleton that regulates red cell morphology and mechanical stability. The purpose of this study was to investigate the genome of a Korean patient with HE to discover the causative gene mutation using gene panel sequencing. Methods: An 89-year-old female presented to the Emergency Department and was diagnosed with pancreatitis and gallstones. A peripheral blood smear revealed that approximately 60% of the RBCs were abnormally shaped and appeared oval or elongated, from slightly egg-shaped to rod or pencil forms (elliptocytes). Targeted gene panel sequencing consisting of 33 genes related to inherited RBC disorders and Sanger sequencing were performed. Results: A heterozygous c.2112G > A of the EPB41 gene leading to premature termination codon (NM_001166005.1:c.2112G > A, p.Trp704*) was identified. This variant, which had not been previously reported to be related to HE, was confirmed by Sanger sequencing. Thus, the patient's diagnosis of HE-1 was genetically confirmed. Conclusion: The present study confirmed a novel mutation of the EPB41 gene that plays an important role in expanding the mutational distribution in HE-1. It could also be helpful for understanding the correlation between the genotype and phenotype in HE.
Asunto(s)
Proteínas del Citoesqueleto/genética , Eliptocitosis Hereditaria/genética , Proteínas de la Membrana/genética , Mutación Puntual , Anciano de 80 o más Años , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/patología , Eritrocitos Anormales/metabolismo , Eritrocitos Anormales/patología , Femenino , Humanos , República de CoreaRESUMEN
BACKGROUND: Familial distal renal tubular acidosis (dRTA) associated with mutations of solute carrier family 4 membrane - 1 (SLC4A1) gene could co-exist with red cell membrane abnormality, Southeast Asian ovalocytosis (SAO). Although this association is well described in Southeast Asian countries, it is less frequently found in Sri Lanka. CASE PRESENTATION: We describe six patients who had dRTA co-existing with SAO. All of them initially presented with severe hypokalemia and paralysis. They presented within a period of six months to the Teaching Hospital Anuradhapura, Sri Lanka. All had metabolic acidosis indicated by low serum bicarbonate. Three of them were having underlying chronic kidney disease as well. Those three patients had mixed high and normal anion gap metabolic acidosis indicated by low delta ratio. In all dRTA was confirmed by presence of normal anion gap, hyperchloraemia, high urine pH and positive urine anion gap. Examination of blood films of all of them revealed presence of stomatocytes and macro-ovalocytosis compatible with SAO. In relation to complications of dRTA, two patients had medullary nephrocalcinosis. Three patients had biochemical evidence of osteomalacia, with two of them having radiological evidence of diffuse osteosclerosis. One patient had secondary hyperparathyroidism and a pathological fracture. CONCLUSIONS: Erythrocyte in SAO is exceptionally rigid and this abnormality is said to be evolved as it protects against Plasmodium vivax malaria and cerebral malaria cause by Plasmodium falciparum. Although two families of SAO was described earlier, SAO and dRTA combination was reported only once in a patient from Anuradhapura district. Distal renal tubular acidosis, SAO combination and its related complications including nephrocalcinosis, chronic kidney disease and metabolic bone disease was not described in Sri-Lankan literature. This case series emphasize the importance of investigating recurrent/ chronic hypokalemia to diagnose dRTA and its associations, as early correction of acidosis could prevent development of chronic kidney disease and metabolic bone disease.
Asunto(s)
Acidosis Tubular Renal/complicaciones , Enfermedades Óseas Metabólicas/complicaciones , Eliptocitosis Hereditaria/complicaciones , Equilibrio Ácido-Base , Acidosis Tubular Renal/sangre , Acidosis Tubular Renal/genética , Adulto , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Bicarbonatos/sangre , Eliptocitosis Hereditaria/sangre , Femenino , Humanos , Hipopotasemia/sangre , Hipopotasemia/complicaciones , Masculino , Persona de Mediana Edad , Osteomalacia/complicaciones , Osteosclerosis , Sri LankaRESUMEN
Dizygotic twin males, born at 34 weeks gestation, had prolonged jaundice, microcytic, hypochromic anemia, FABarts hemoglobin, elevated end-tidal CO, and blood films consistent with hereditary pyropoikilocytosis. DNA sequencing revealed both had a heterozygous alpha spectrin (SPTA1) mutation (c.460_462dup) inherited from their asymptomatic mother, plus a 3-base pair duplication in alpha globin (HBA2) (c.364_366dupGTG) inherited from their asymptomatic father.
Asunto(s)
Anemia Hemolítica/complicaciones , Anemia Hipocrómica/complicaciones , Eliptocitosis Hereditaria/complicaciones , Ictericia/complicaciones , Anemia Hemolítica/sangre , Anemia Hemolítica/genética , Anemia Hipocrómica/sangre , Anemia Hipocrómica/genética , Eliptocitosis Hereditaria/sangre , Eliptocitosis Hereditaria/genética , Humanos , Recién Nacido , Ictericia/sangre , Ictericia/genética , Masculino , Mutación Puntual , Espectrina/genética , Gemelos Dicigóticos/genéticaRESUMEN
Various mutations in the genes encoding alpha spectrin (SPTA1) or beta spectrin (SPTB) are known to cause erythrocyte membrane disorders, sometimes associated with severe neonatal jaundice and anemia. We used a next-generation sequencing panel to evaluate 3 unrelated neonates who had puzzling cases of nonimmune hemolytic jaundice. In each case, we identified novel mutations in either SPTA1 or SPTB. Correlating erythrocyte morphology, clinical course, and computational analysis, we submit that each of the 3 variants is a probable pathogenic cause of the hereditary hemolytic conditions in these patients. We hope other pediatric practitioners caring for neonates with what appears to be idiopathic severe neonatal hyperbilirubinemia will look for spectrin variants as a possible cause, because additional cases with these specific variants along with this clinical phenotype are needed to confirm our postulate that these 3 cases are indeed pathogenic mutations.
Asunto(s)
Eliptocitosis Hereditaria/genética , Ictericia Neonatal/genética , Mutación/genética , Espectrina/genética , Esferocitosis Hereditaria/complicaciones , Adulto , Eliptocitosis Hereditaria/complicaciones , Femenino , Humanos , Recién Nacido , Ictericia Neonatal/complicaciones , Ictericia Neonatal/terapia , Masculino , FototerapiaAsunto(s)
Eliptocitosis Hereditaria/sangre , Eritrocitos Anormales/ultraestructura , Rasgo Drepanocítico/sangre , Trombocitosis/sangre , Talasemia beta/sangre , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Rasgo Drepanocítico/complicaciones , Trombocitosis/complicaciones , Talasemia beta/complicacionesRESUMEN
Hereditary elliptocytosis is an inherited red blood cell membrane disorder characterized by typical peripheral blood smear findings of elliptocytes or rod-like red blood cells. Hemoglobin H disease is a form of α-thalassemia disease resulting in mild to moderate hemolytic anemia. The authors report 1 case of a girl who was diagnosed with oculo-auriculo-vertebral spectrum and a coinheritance of hereditary elliptocytosis and deletional hemoglobin H disease. She had moderate, non-transfusion-dependent anemia. The red blood cells showed marked poikilocytosis and fragmentation. The parents were α-thalassemia carriers and the father had the typical red blood cell morphology of common hereditary elliptocytosis.
Asunto(s)
Eliptocitosis Hereditaria/complicaciones , Síndrome de Goldenhar/complicaciones , Eliminación de Secuencia , Globinas alfa/genética , Talasemia alfa/complicaciones , Adulto , Preescolar , Eliptocitosis Hereditaria/genética , Eritrocitos Anormales , Femenino , Genotipo , Humanos , Hiperbilirrubinemia Neonatal/etiología , Masculino , Talasemia alfa/genéticaAsunto(s)
Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/diagnóstico , Sobrecarga de Hierro/diagnóstico , Sobrecarga de Hierro/etiología , Talasemia beta/complicaciones , Talasemia beta/diagnóstico , Biomarcadores , Eliptocitosis Hereditaria/terapia , Índices de Eritrocitos , Duplicación de Gen , Humanos , Sobrecarga de Hierro/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Mutación , Fenotipo , Reacción en Cadena de la Polimerasa , Globinas alfa/genética , Globinas beta/genética , Talasemia beta/terapiaRESUMEN
We report a 60-year-old adult case with a normocytic normochromic regenerative anemia discovered incidentally. The objectification of elliptocytosis accompanied by splenomegaly, a collagen myelofibrosis and the presence of the mutation JAK2V617F allowed the diagnosis of primary myelofibrosis with atypical initial presentation. The causes of elliptocytoses are discussed.
Asunto(s)
Anemia/diagnóstico , Eliptocitosis Hereditaria/diagnóstico , Anemia/complicaciones , Anemia/genética , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/genética , Humanos , Hallazgos Incidentales , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Mutación , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/genéticaAsunto(s)
Eliptocitosis Hereditaria/diagnóstico , Eritrocitos Anormales/ultraestructura , Ictericia Neonatal/etiología , Consanguinidad , Eliptocitosis Hereditaria/sangre , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/terapia , Transfusión de Eritrocitos , Humanos , Recién Nacido , Ictericia Neonatal/terapia , Masculino , FototerapiaAsunto(s)
Anemia Refractaria con Exceso de Blastos/patología , Proteínas del Citoesqueleto/genética , Eliptocitosis Hereditaria/patología , Proteínas de la Membrana/genética , Neuropéptidos/genética , Anciano , Anemia Refractaria con Exceso de Blastos/complicaciones , Anemia Refractaria con Exceso de Blastos/genética , Médula Ósea/patología , Aberraciones Cromosómicas , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/genética , Femenino , Eliminación de Gen , Humanos , Cariotipo , Neutrófilos/patologíaRESUMEN
Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy.