A REVIEW ON CURRENT TREATMENT OF FANCONI ANEMIA

*Poonam Pandhari Jawarkar, Laxmi Suresh Ghatol, Bhavika Ambadas Sapkal, Ankit Vinod Chikte, Prof. P. N. Folane and Dr. R. H. Kale, Dr. K. R. Biyani

ABSTRACT

This review summarises the clinical features of Fanconi Anemia and the natural history of the disease, discusses diagnosis and management, and puts the recent molecular advances into the context of the cellular and clinical Fanconi anemia phenotype. Fanconi Anemia is a rare, genetic heterogeneous multisystem disease that is the most common congenital syndrome of marrow failure. The much increased risk of FA Patients developing leukaemia and squamous cell carcinomas makes FA an important model disease for cancer predisposition. Fanconi anemia patients are characterized by pancytopenia, congential malformations, growth delay and an increased susceptibility to the development of malignancies, particularly acute myelogenous leukemia. Fanconi anemia is caused by the genetic interruption of cellular pathway that repairs DNA interstrand crosslinks. The impaired function of this pathway, and the genetic instability that results, is considered the main pathogenic mechanism behind the disease. It is mostly autosomal (except one X-link) recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both haematological malignancy and solid tumors. Although this highly variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, laboratory study of chromosomal breakage induced by diepoxybutane (DEB) or other crosslinking agents provides a unique cellular marker for the diagnosis of the disorder either prenatally or postnatally. Diagnosis based on abnormal response to DNA crosslinking agents can be used to identify the pre - anemia patient as well as patients with aplastic anemia or leukemia who may or may not have the physical stigmata associated with the syndrome. This overview will present our present knowledge regarding the varied phenotypic manifestation of FA and procedures for diagnosis based upon abnormal DNA damage responses. Chromosomal instability, especially an exposure to alkylating agents, may be shown in affected subjects and is the basis for a diagnostic test. FA can be caused by mutations is at least seven different genes. Interaction pathways have been established, both between the FA proteins and other proteins involved in DNA damage repair, such as ATM, BRCA1 and BRCA2, thereby providing a link with other disorders in which defective DNA damage repair is a feature.

Keywords: Chromosomal Instability, Congenital Anomalies, Hematologic Abnormalities, DNA crosslink sensitivity, Somatic mosaicism.