Bhandari Jenish, Thada Pawan K., Killeen Robert B., Puckett Yana
SUNY Upstate Medical University
Punjab Medical College/University of Health Sciences
Fanconi anemia is the most common cause of inherited bone marrow failure due to a rare autosomal recessive genetic disorder involving all 3 blood cell lines in which homozygous or heterozygous mutations result in pathogenic alleles, including point mutations, duplications, splicing defects, and deletions. These genetic mutations of Fanconi anemia genes cause an accruement of chromosomal damage due to the cell's inability to conduct repairs. Typically, Fanconi anemia proteins maintain genomic integrity and replicative capacity through DNA interstrand crosslinks (ICLs) repair. ICLs prevent DNA strand separation and maintain DNA integrity. These genetic mutations in the Fanconi anemia pathway lead to cells that cannot properly repair DNA damage, resulting in genomic instability, subsequent pancytopenia, and an increased susceptibility to cytotoxic agents, ultraviolet radiation, spontaneous deformation, and predisposition to malignancies. Additionally, Fanconi anemia affects almost all organs of the body. Fanconi anemia is also thought of as an inherited form of aplastic anemia. Extensive studies of other bone marrow failure syndromes and chromosome fragility diseases have enhanced the scientific understanding of bone marrow failure in Fanconi anemia. Common clinical symptoms of Fanconi anemia include shortness of breath, chest pain, dizziness, and fatigue. Additionally, a clinical history of epistaxis, petechiae, and excessive bleeding from a wound site is common due to thrombocytopenia. The condition is mainly associated with other congenital deformities and is usually more common during childhood, with the average age of diagnosis being 7 years. Structural extremity abnormalities are more commonly observed on physical exams in patients with Fanconi anemia. The disorder may also predispose patients to the development of hematologic and solid tumors. Pancytopenia characteristic of Fanconi anemia is usually evident in serum laboratory studies demonstrating a decrease in all 3 blood cell lines, including red blood cells (RBCs), platelets, and leukocytes. Fanconi anemia should be evaluated in patients presenting with signs and symptoms of pancytopenia with or without characteristic malformations and in patients with a family history of bone marrow failure or unbalanced translocations identified during a diagnostic leukemia evaluation. Furthermore, Fanconi anemia should be considered in patients with early-onset tumors or excessive toxicity after standard-dose chemotherapy. A Fanconi anemia diagnosis is typically confirmed with a chromosomal fragility test, which remains the gold standard. Management of Fanconi anemia primarily includes supportive therapy, hematopoeitic stem cell transplantation, and androgen treatment.
范可尼贫血是遗传性骨髓衰竭最常见的病因，它是一种罕见的常染色体隐性遗传病，累及所有三种血细胞系，纯合或杂合突变会产生致病等位基因，包括点突变、重复、剪接缺陷和缺失。范可尼贫血基因的这些基因突变会导致染色体损伤的累积，因为细胞无法进行修复。通常，范可尼贫血蛋白通过DNA链间交联（ICL）修复来维持基因组完整性和复制能力。ICL可防止DNA链分离并维持DNA完整性。范可尼贫血通路中的这些基因突变会导致细胞无法正确修复DNA损伤，从而导致基因组不稳定、随后的全血细胞减少，以及对细胞毒性药物、紫外线辐射、自发变形的易感性增加，以及患恶性肿瘤的倾向。此外，范可尼贫血会影响身体几乎所有器官。范可尼贫血也被认为是再生障碍性贫血的一种遗传形式。对其他骨髓衰竭综合征和染色体脆性疾病的广泛研究增进了对范可尼贫血中骨髓衰竭的科学认识。范可尼贫血的常见临床症状包括呼吸急促、胸痛、头晕和疲劳。此外，由于血小板减少，鼻出血、瘀点和伤口部位过度出血的临床病史很常见。该病症主要与其他先天性畸形有关，通常在儿童期更常见，平均诊断年龄为7岁。在对范可尼贫血患者进行体格检查时，更常观察到肢体结构异常。该病症还可能使患者易患血液系统和实体肿瘤。范可尼贫血特有的全血细胞减少通常在血清实验室研究中很明显，显示所有三种血细胞系减少，包括红细胞（RBC）、血小板和白细胞。对于出现全血细胞减少体征和症状（有或无特征性畸形）的患者，以及在诊断性白血病评估中发现有骨髓衰竭或不平衡易位家族史的患者，应评估是否患有范可尼贫血。此外，对于早发性肿瘤患者或标准剂量化疗后出现过度毒性的患者，也应考虑范可尼贫血。范可尼贫血的诊断通常通过染色体脆性试验来确认，该试验仍然是金标准。范可尼贫血的治疗主要包括支持治疗、造血干细胞移植和雄激素治疗。
