Clinical and cytogenetic profile of Fanconi anemia diagnosed after implementation of mitomycin C cytogenetic test in the state of Pernambuco, Brazil

ABSTRACT Introduction: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosomal instability and increased predisposition to malignancy. The diagnosis of FA requires clinical evaluation, confirmation of chromosomal fragility and/or analysis of genetic mutations. Therefore, this study aims to identify the clinical profile of patients with FA in the state of Pernambuco, Brazil. Method: We analyzed 100 individuals referred from the major hematology and bone marrow (BM) transplant centers in the state of Pernambuco, Brazil, between the years 2018 and 2022. The diagnosis of FA was performed using the mitomycin C chromosomal fragility test, clinical data and classical and molecular cytogenetic analyses. Results: We enrolled a total of 16 patients with FA to comprise this study. Most of these individuals (87.5%) came from the Agreste and Sertão regions of Pernambuco. We observed a slight female prevalence of FA (1.3:1). The primary clinical and laboratory findings were café au lait spots (62.5%) and bone abnormalities (53%, mainly thumb deformities [40%]). We performed BM cytogenetic analysis for eight patients - seven showed no chromosomal abnormalities and one presented the karyotype 47,XY,+21 [15]. Conclusions: Our results are important to promote public health measures for the early diagnosis of FA, as well as to foster the engagement of a multidisciplinary group in the treatment of this disease.

Clinical and cytogenetic profile of Fanconi anemia diagnosed after implementation of mitomycin C cytogenetic test in the state of Pernambuco, Brazil.

INTRODUCTION: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosomal instability and increased predisposition to malignancy. The diagnosis of FA requires clinical evaluation, confirmation of chromosomal fragility and/or analysis of genetic mutations. Therefore, this study aims to identify the clinical profile of patients with FA in the state of Pernambuco, Brazil. METHOD: We analyzed 100 individuals referred from the major hematology and bone marrow (BM) transplant centers in the state of Pernambuco, Brazil, between the years 2018 and 2022. The diagnosis of FA was performed using the mitomycin C chromosomal fragility test, clinical data and classical and molecular cytogenetic analyses. RESULTS: We enrolled a total of 16 patients with FA to comprise this study. Most of these individuals (87.5%) came from the Agreste and Sertão regions of Pernambuco. We observed a slight female prevalence of FA (1.3:1). The primary clinical and laboratory findings were café au lait spots (62.5%) and bone abnormalities (53%, mainly thumb deformities [40%]). We performed BM cytogenetic analysis for eight patients - seven showed no chromosomal abnormalities and one presented the karyotype 47,XY,+21 [15]. CONCLUSIONS: Our results are important to promote public health measures for the early diagnosis of FA, as well as to foster the engagement of a multidisciplinary group in the treatment of this disease.

Colelitíase no paciente pediátrico portador de doença falciforme: [revisão] / Cholelithiasis in children with sickle cell disease: [review]

OBJETIVO: Considerando a alta freqüência da colelitíase no paciente pediátrico com doença falciforme e a controvérsia na literatura sobre a abordagem da condição, o presente texto objetiva revisar a literatura disponível. FONTE DE DADOS: Revisão dos estudos sobre colelitíase no paciente falciforme, publicados no período entre 1980 e 2007, em língua inglesa e portuguesa, envolvendo pacientes na faixa etária de zero a 18 anos e utilizando os bancos de dados Medline e Lilacs. SÍNTESE DOS DADOS: A colelitíase é a complicação digestiva mais comum no paciente falciforme e sua incidência aumenta com a faixa etária. Os mecanismos fisiopatológicos são conhecidos, assim como os métodos diagnósticos. A conduta terapêutica consensual na colelitíase sintomática é a colecistectomia, preferencialmente por via laparoscópica. Nos casos assintomáticos, a maioria dos autores recomenda a conduta cirúrgica, para evitar complicações, confusão no diagnóstico diferencial de dor abdominal futura e menor risco cirúrgico. Contudo, não existe consenso na literatura, havendo base para a adoção de conduta expectante. CONCLUSÕES: A doença falciforme tem grandes variações em sua apresentação clinica, história natural e gravidade da hemólise. Algumas populações podem apresentar menor freqüência de colelitíase e menor número de pacientes sintomáticos, possivelmente em razão de variações de haplótipos, fatores ambientais e diferentes manejos clínicos. Ainda não existem dados suficientes na literatura ou estudos randomizados e controlados que possibilitem definir o momento ideal para a colecistectomia no paciente falciforme com litíase assintomática. Dessa maneira, dependendo de características individuais e da população, podem ser aceitos o seguimento clínico ou a indicação precoce de colecistectomia.

OBJECTIVE: Given the high frequency of cholelithiasis in children with sickle cell disease and the controversies about its management, the aim of this study was to critically review the literature about this issue. DATA SOURCES: Published studies in English and Portuguese from 1980 to 2007 about cholelithiasis and sickle cell anemia in children were retrieved from Medline and Lilacs databases. DATA SYNTHESIS: Cholelithiasis is the most common digestive complication of sickle cell disease patients and its frequency increases with age. Physiopathology of gallstones and diagnostic methods are well established. Cholecystectomy is the recommended therapy for symptomatic cholelithiasis, preferentially by laparoscopic approach. In asymptomatic patients, most studies favors the surgical management of the disease in order to avoid complications and to reduce difficulties with the differential diagnosis of future abdominal pain. However, the clinical management of this condition is also possible and there is no consensus in the literature regarding the best approach. CONCLUSIONS: Sickle cell disease presents great variations in clinical presentation, natural history and severity of hemolysis. Some populations may present lower frequency of cholelithiasis and its symptoms. Variability in the frequency of this complication may be attributed to genetic variation in haplotipes, environmental factors, clinical course and management of the sickle cell disease. Scientific evidence regarding the best time to indicate cholecystectomy in asymptomatic patient is not available. Therefore, decision regarding the need of clinical or surgical approach of the cholelithiasis depends on individual and population factors.