Diagnosis of Fanconi anemia - a clinical practice challenge

Introduction: Fanconi anaemia is a rare genetic disorder with autosomal recessive or X-linked reces­sive inheritance. This condition is characterized by multiple gene mutations leading to errors in DNA replication and manifests with progressive pancytopenia, bone marrow failure, multiple congenital malformations and predisposition to malignancies. Materials and methods: The patient is a 4-year-old male, born preterm at 36 weeks with a weight of 2220g and a length of 43cm. At birth multiple skeletal anomalies were found -right radial aplasia, bi­lateral absence of metacarpal and phalangeal bones of the first row, as well as radial deviation of the right metacarpal bones and improper alignment of the left metacarpal bones. Facial dysmorphism, atrial septal defect and single hypopigmented macules were also observed. At the age of 3 the patient was diagnosed with hypopituitarism, due to clinical and laboratory evidences of hypogonadism, sec­ondary hypothyroidism and growth hormone deficiency he was treated with L-Thyroxine and growth hormone for a year. Results: During a routine clinical examination a hemorrhagic rash of the lower limbs was found which required the implementation of a haemogram, biochemistry test and bone marrow biopsy with flow cytometry. The results revealed signs of moderate to severe anemia, and Stage III - IV thrombo­cytopenia, as well as a hypocellular bone marrow without cytomorphological and flowcytometrical signs of clonal proliferation. These deviations from the normal hematological values combined with all existing physical abnormalities and short stature led to the consideration of Fanconi anemia in the differential diagnosis. Diepoxybutane (DEB) analysis was performed, proving chromosome breakage and deletions in 3rd, 7th, 12th and 13th chromosomes. Conclusion: Fanconi Anemia is a rare hereditary disorder with a poor prognosis. Well-timed diag­nostics allows early bone marrow transplantation, which can improve complications and reduces the risk of cancer development.