This is a rare disorder that results in bone marrow failure. Most of the individuals with this condition are diagnosed before the age of 10 and present various abnormalities such as the skin pigmentation, small eyes, abnormal kidney structures and skeletal anomalies. These individuals exhibit the deficiency of all the types of blood cells that are produced by the bone marrow such as the red blood cells, white blood cells and the platelets. The red blood cells are responsible for the delivery of oxygen to various tissues of the body, white blood cells are essential to fight off infections and the platelets are required for the blood clotting in the case of an injury. As the result, these cases often experience fatigue, recurrent infections and clotting problems. This condition is estimated to affect around 1 in 160,000 people globally and appears to be more prevalent among the population of the Ashkenazi Jewish descent, the black South Africans and the Roma population.
Symptoms
This condition is evident at birth with various physical defects such as the hand and the arm anomalies that can include the missing or extra thumbs, or the missing radius, skeletal anomalies, mental retardation, small reproductive organs in males, problems with the heart, small head or eyes, gastrointestinal difficulties, kidney problems and skin discoloration. These affected individuals are also at increased risk of developing cancer known as acute myeloid leukemia or the tumors of the skin, genital tract, the head and the neck.
Causes
Fanconi anemia can develop as the result of the mutation in at least 15 genes which are necessary for the production of a protein that is involved in a process known as the FA pathway. This is essential for the delivery of certain proteins that trigger the DNA repair so that new copies of DNA can be made in a process known as DNA replication. Around 90% of the cases of fanconi anemia develop as the result of the mutation in one of the three genes identified as FANCA, FANCC and FANCG. The mutation in the gene affects the FA pathway and as the result, the DNA damage is not effectively repaired. Hence, the abnormal cell death or the uncontrolled cell growth occurs. This condition is mostly inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell from the parents are defective. However, this condition can also be inherited in an X-linked recessive pattern where the defective gene is located in one of the sex chromosomes and hence male population tends to be more affected than the females.
Diagnosis
The diagnosis is based on the identification of the features that are characteristic of this condition, various tests and a thorough clinical evaluation. The tests include the chromosome breakage test and blood analysis to identify the level of blood cells and platelets. The X-rays help to determine the extent of skeletal abnormalities and internal structural problems.
Treatment
The treatment focuses on the various symptoms that are evident in each individual. The treatment for this condition may involve the coordination of various specialists such as the pediatricians, kidney specialist (nephrologists), gastroenterologists, cardiologist and surgeons who can devise an effective treatment plan for the individual. The treatment options include surgery to correct the skeletal conditions, cancer treatment for any malignancies that may develop or hematopoietic stem cell transplantation.
References
https://rarediseases.org/rare-diseases/fanconi-anemia/
https://ghr.nlm.nih.gov/condition/fanconi-anemia#inheritance
http://fanconi.org/index.php/learn_more/diagnosis
