ABSTRACT
Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.
Subject(s)
Child , Male , Humans , Female , Infant , Child, Preschool , Retrospective Studies , Neoplasm Proteins/genetics , Optic Atrophy/genetics , Pelger-Huet Anomaly/genetics , Liver Failure, Acute/complicationsABSTRACT
OBJECTIVE@#To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly (PHA) and to explore its clinical characteristics.@*METHODS@#Genomic DNA was extracted from the pedigree and healthy controls. The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified in other family members and 100 healthy controls. Polyphen-2 and SIFT software were used to predict the effect of the mutation, and Swiss-model software was used to simulate the protein structure.@*RESULTS@#Three patients were found to carry a c.893G>A mutation in exon 8 of the LBR gene, which resulted in substitution of the 298th amino acid residue glycine by glutamic acid (p.Gly298Glu). The same mutation was not found in healthy family members and 100 healthy controls. The mutation was predicted to be damaging. Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein.@*CONCLUSION@#The c.893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.
Subject(s)
Humans , Case-Control Studies , DNA Mutational Analysis , Exons , Mutation , Pedigree , Pelger-Huet Anomaly , Genetics , Polymerase Chain Reaction , Receptors, Cytoplasmic and Nuclear , GeneticsABSTRACT
La anomalía de Pelger Hüet fue descrita inicialmente en 1928 por el médico holandés Pelger y su origen genético fue descubierto más tarde por el pediatra Hüet. Se transmite con un carácter autosómico dominante y consiste en una mutación del gen que codifica el receptor de la lámina B. A partir de esta mutación se producen alteraciones en el núcleo de los leucocitos, fundamentalmente en los neutrófilos, con afectación de la segmentación nuclear y trastornos en la cromatina. Presentamos a un paciente que fue ingresado en el hospital por una mordedura de animal y se describió en la lámina periférica la presencia de neutrófilos hipolobulados. El carácter familiar se confirmó por el hallazgo de esta alteración en la madre del paciente.
The Pelger-Hüet anomaly was described firstly in 1928 by the Holland physician Pelger and its genetic origin was discovered later by the pediatrician Hüet. It is transmitted with a dominant autosomal character and it is a mutation of the gene codifying the plate B receptor. Beginning from this mutation, the alteration of white cells core took place, mainly in neutrophils, with affectations of the nuclear segmentation and chromatin disturbances. We present a patient entering our hospital as a cause of an animal bite, and there were discovered hypolobulated neutrophils in the periferal plate. The familiar character was confirmed with the finding of this alteration in the patient's mother.
Subject(s)
Humans , Child , Pelger-Huet Anomaly/diagnosis , Pelger-Huet Anomaly/genetics , Pelger-Huet Anomaly/blood , Case ReportsABSTRACT
The Pelger-Huët anomaly is a dominant autosomal disease, characterized by the incomplete segmentation of the granulocytes nucleus without lost of the cellular function. The heterozygotes form of this anomaly is assintomatic and it did not possess physic meant, while the homozygote form is rare and can be lethal, being therefore, important differentiates of other infectious alterations. The pseudo-anomaly can occasionally be observed in cases of granulocitic leukemia, mieloproliferatives Diseases, some infections and after exposition the determined drugs. We evaluate eleven members of a familiar nucleus and, after the blood cells analysis, six of then had presented neutrophils and eosinophils with nuclei characteristic of the heterozygotes form of the Pelger-Huët anomaly. The recognition of this leukocyte anomaly, mainly in patients without infection and presenting great number of not segmented neutrophils, can prevent wrong interpretations of the blood cells count and unnecessary clinical and therapeutically behaviors.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Pelger-Huet Anomaly/genetics , Leukocytes/pathology , Pelger-Huet AnomalyABSTRACT
Impaired lobulation of neutrophils together with exaggerated clumping of chromatin, characteristic of Pelger-Huet anomaly was seen as an incidentalfinding in a 43-year old man who presented with depression. Peripheral blood and bone marrow findings and cytochemistry of the abnormal cells are described and the disease entity discussed.
Subject(s)
Adult , Bone Marrow Examination , Humans , Male , Neutrophils/pathology , Pelger-Huet Anomaly/bloodABSTRACT
La anomalía de Pelger-Huet se observa una limitación de la segmentación nuclear de los granulocitos. La anomalía fue descrita por primera vez por Pelger en 1928, quien consideró que constituía una manifestación de tuberculosis. Huet consideró que la anomalía sería hereditaria y se transmitiría en forma autonómica dominante. Los individuos afectados rara vez presentan neutrófilos o eosinófilos con más de dos lóbulos. En los heterocigotos, el núcleo de los neutrófilos es no segmentado, con forma de pesa o bilobulado. En los homocigotos, la gran mayoría de los neutrófilos presentan núcleos redondos. Esta anomalía afecta aproximadamente a uno de cada 6000 individuos. La migración celular puede estar levemente alterada, pero la función de los granulocitos es normal y los individuos con esta anomalía hereditaria no padecen efectos adversos. Se trata de Rn masculino quien a las pocas horas de vida presenta ictericia neonatal y dificultad respiratoria y hepatoesplenomegalia. Hallazgos paraclínicos incompatibilidad de grupo sanguíneo, reacción leucemoide 98000 globulos blancos, PCR (-), e hiperbilirrubinemia a predominio de la indirecta. Se indica fototerapia, Oxigeno, y antibioticoterapia a base de PNC, Amikacina y vancomicina, Se realiza serología para TORCHS la cual reporta negativa y valoración por hematología la cual reporta anomalía de Pelger-Huet. Se presenta este caso para dar a conocer la existencia de esta anomalía como causa de errores frecuenctes al momento de valorar la hematología en procesos infecciosos y no infecciosos, que reportan reacciones leucemoides. Es importante que tanto el médico tratante como el paciente, esten en conocimiento de esta anomalía sanguínea, para valorar de forma adecuada el hemograma en posteriores oportunidades.
Subject(s)
Humans , Adult , Female , Pregnancy , Amikacin/administration & dosage , Pelger-Huet Anomaly/genetics , Pelger-Huet Anomaly/pathology , Erythroblastosis, Fetal/diagnosis , Splenomegaly/pathology , Jaundice, Neonatal/diagnosis , Vancomycin/administration & dosage , Amikacin/pharmacology , Hypoxia/therapy , Phototherapy/methodsSubject(s)
Adenocarcinoma/blood , Aged , Blood Sedimentation , Colectomy , Colonic Neoplasms/blood , Colonoscopy , Female , Humans , India , Neoplasm Staging , Neutrophils/ultrastructure , Pedigree , Pelger-Huet Anomaly/bloodABSTRACT
Os autores apresentam quatro individuos com a anomalia de Pelger-Huet, em duas familias. Dois dos pacientes foram encaminhados para diagnostico de infeccao devido a interpretacao erronea de hemograma. Os outros dois eram parentes de um dos casos-indices. Os autores enfatizam a importancia do diagnostico da anomalia para nao se incorrer em condutas diagnosticas e terapeuticas desnecessarias
Subject(s)
Humans , Male , Female , Pelger-Huet Anomaly/diagnosis , Hematologic Diseases/diagnosis , Leukocyte Count , Pelger-Huet Anomaly/pathology , Leukocytes/pathology , Tuberculosis/etiologyABSTRACT
A anomalia de Pelger-Huet e uma alteracao leucocitaria autossomica dominante, caracterizada pela segmentacao incompleta do nucleo dos neutrofilos e eosinofilos. A forma heterozigoto em geral e assintomatica, com prevalencia que varia de 1:1.000 a 1:10.000 pessoas, podendo acometer caucasoides, negroides e orientais. A forma homozigoto e extremamente rara, algumas vezes letal. Os autores estudaram o sangue periferico de uma familia de dez pessoas, sete portadoras desta anomalia, nas quais os neutrofilos e eosinofilos apresentaram nucleos com aspecto em "casca de amendoim" e "oculos" (pince-nez), com cromatina mais densa. No heredograma e ilustrada a distribuicao da anomalia nos individuos portadores. O reconhecimento desta anomalia leucocitaria nos hemogramas e importante, pois evita interpretacoes clinicas erroneas, como o "desvio a esquerda" por causa infecciosa
Subject(s)
Pelger-Huet Anomaly/diagnosis , LeukocytesABSTRACT
La anomalía de Pelger-Huët es una alteración benigna en la forma de los granulocitos que se hereda principalmente en forma autosómica dominante. La prevalencia de esta anomalía varía de país a país y en México está sería la sexta familia informada. Se presenta el caso de un niño de un año nueve meses de edad que fué detectado durante el estudio de anemia ferropénica con la cual se presentó al hospital; en su familia, de nueve miembros, se encontró la afección únicamente en el padre del paciente. Se practicó estudio de microscopía electrónica a los neutrófilos del padre del propositus y de un testigo normal; se encontró que los gránulos del paciente y su padre eran de tamano normal pero estaban disminuidos en cantidad. Se discute el modo de herencia, la presentación, la morfología, el diagnóstico diferencial y se enfatiza la importancia de reconocer esta anomalía y practicar consejo genético
Subject(s)
Chromosome Aberrations/diagnosis , Genetics, Medical/methods , Pelger-Huet Anomaly , Genetic Techniques/trends , Chromosome Aberrations/immunology , Genetics, Medical , Genetic Techniques/instrumentationABSTRACT
Se informa de los hallazgos realizados en forma incidental en uno de los miembros de una familia mexicana con anomalía de Pelger-Huët. De los 29 familiares estudiados, 12 presentaron esta alteración. El diagnóstico de esta anomalía se establece en el estudio del frotis en sangre periférica y se confirma cuando varios miembros de una familia están afectados
Subject(s)
Child, Preschool , Child , Adolescent , Adult , Middle Aged , Humans , Male , Female , Pelger-Huet Anomaly/genetics , Granulocytes/ultrastructureABSTRACT
Se presenta el caso de un paciente del sexo masculino, con anomalia leucocitaria de Pelger-Huet, entidad hereditaria que se transmite en forma autosomica dominante, caracterizada por segmentacion incompleta de los nucleos de los leucocitos y condensacion anormal de la cromatina nuclear.Se discuten las caracteristicas clinicas y de evolucion de esta enfermedad, enfantizandose en su frecuencia de presentacion y en el consejo genetico que debe ser proporcionado a los pacientes detectados