Fanconi Anemia (FA)

Fanconi Anemia
Body Parts: Whole Body
Medical Subjects: Children's Health Blood Genetic disease

What Is Fanconi Anemia?

Fanconi anemia (FA) is a rare genetic syndrome, which is mainly associated with genomic instability. The clinical manifestations are diverse, including hematopoietic failure (pancytopenia), multiple congenital malformations, hearing impairment, hypogonadism and hyperpigmentation of the skin. Moreover, patients are prone to hematological malignancies and solid tumors.

FA mostly occurs in childhood, but the diagnosis of the disease lags behind. The patient cannot be diagnosed definitively until bone marrow failure occurs. The diagnosis of FA is mainly based on clinical manifestations and laboratory tests. Current treatment regimens include androgen therapy, hematopoietic stem cell transplantation, and gene therapy, which may result in patient death if not managed in time. The prognosis is poor.

Fanconi anemia is uncommon and has an incidence of approximately 1/1 million to 5/1 million.


What Is The Cause Of Fanconi Anemia?

Fanconi anemia is not contagious, but current research shows that Fanconi anemia is actually a hereditary disease, and genetic abnormalities cause patients' cells to be unable to correctly repair a particularly harmful DNA damage, namely, inter-chain crosslinking (ICL). The majority of FA cases are autosomal recessive. There are many genes involved, and the genes most frequently mutated are FANCA, FANCC, and FANCG.


What Is The Symptoms Of Fanconi Anemia?

What are the common manifestations of Fanconi anemia?

FA mostly occurs in childhood. Its performance is as follows:

Congenital malformations and endocrine abnormalities:

  • Congenital malformations and intellectual developmental disorders account for 70% of the clinical manifestations in patients with FA. As we get older, patients with FA may present with developmental delay, manifested as short stature, microcephaly, small eyeball, pigmented skin, undeveloped or absent thumb or radius, multiple fingers, webbed fingers, etc.
  • Some patients may have reproductive system hypoplasia, for example, 50% female patients may have infertility, and pregnant women with FA are prone to complications (eclampsia, premature birth). For male patients, gonadal agenesis, external genital deformity and reduction of sperm count are common.

Progressive bone marrow failure: Anemia is an important clinical feature in patients with FA, presenting with monocytic or pancytopenia, giant cell anemia, and increased fetal hemoglobin. Later, bone marrow proliferation gradually decreased, most notably the decrease of megakaryocytes. At an advanced stage of the disease, approximately 90% of patients with FA die of bone marrow failure. However, more than 30% of patients lack the typical symptoms mentioned above, which easily leads to the delay of diagnosis.

Secondary tumors: Secondary tumors that may occur in patients with FA include malignant hematological tumors and solid tumors. Such as hematological tumor such as acute myeloid leukemia, acute lymphoblastic leukemia and lymphoma and squamous cell carcinoma (esophageal cancer and vaginal canc), head and neck cancer cerebroma, astrocytoma, liver cancer, nephroblastoma and breast solid tumor.

How does Fanconi anemia develop?

Fanconi anemia occurs more often than in childhood, and it progresses continuously and deteriorates gradually.

What other diseases may be complicated by Fanconi anemia?

Developmental deformity, mental retardation, developmental delay, infertility, bone marrow failure, malignant blood tumor and solid tumor, etc.


How To Check Fanconi Anemia?

How to diagnose Fanconi anemia?

The diagnosis of FA is often delayed, and most children are diagnosed between the ages of 6 and 9 years, when bone marrow failure occurs. Therefore, special attention should be paid to the early detection and diagnosis of FA. The International FA Research Foundation proposed primary and secondary conditions for diagnosis.

Main conditions:

  • Positive family history.
  • Bone marrow aplasia.
  • Characteristic congenital malformation.
  • Spontaneous chromosome rupture.
  • Myelodysplastic syndrome MDS in children.
  • Acute myeloid leukemia in children.
  • Is extremely sensitive to chemo (radiation) therapy.
  • Family history with breast or other tumors.

Secondary conditions:

  • Family history of pancytopenia.
  • Large cell anemia that cannot be explained by vitamin B12 and folic acid deficiencies.
  • Liver tumors of non-hepatitis and non-alcoholic hepatitis.
  • The patient was < 30 years old and had ovarian failure.
  • The patient was < 5 years old and a brain tumor was diagnosed.
  • Nephroblastoma was diagnosed in a patient < 5 years of age.
  • Unexplained increases in HbF.
  • Male/female infertility.

The diagnosis of FA is difficult, especially in patients without obvious congenital malformations, intellectual development disorders, bone marrow failure and secondary tumors.

What tests are needed to diagnose Fanconi anemia?

The common laboratory diagnostic methods for FA include chromosome break test, gene mutation analysis, bone marrow chromosome analysis, and single cell gel electrophoresis.

  • Chromosome break test is a common method for FA primary screening, but it can give a false positive result. If the result of chromosome break test is positive, gene mutation detection is required.

  • Bone marrow chromosome analysis is to detect whether there is chromosome abnormal clone in FA patients by chromosome G banding technology. The G banding technology has been widely used due to its low cost and mature technology.

  • In addition, the fluorescence in situ hybridization technique, the spectral karyotype analysis technique and the gene chip detection can also be applied to the bone marrow karyotype analysis.

Which diseases are easily confused with Fanconi anemia?

It can be confused with bone marrow failure syndrome, chromosome instability syndrome, hereditary diseases of congenital malformations and mental retardation, acute leukemia in adolescents, and neoplasms.

Doctors need to make the difference by doing tests such as chromosome breakage tests.


How To Prevent Fanconi Anemia?

Can Fanconi anemia be prevented?

Fanconi anemia cannot be prevented. Fanconi anemia is a hereditary disease, the etiology of which is still unclear and there is no specific method of prevention. It is suggested that the recognition of FA should be improved, attention should be paid to family history, especially for similar patients in compatriots, and effective detection of chromosome break should be carried out, which will contribute to the early diagnosis.


How To Treat Fanconi Anemia?

Fanconi anemia cannot be cured by itself. Patients with Fanconi anemia should go to pediatrics or hematology department.

Current treatment options include androgen therapy, hematopoietic stem cell transplantation, and gene therapy.

  • Gene therapy scheme: Although it can improve bone marrow failure in patients with FA, FA is caused by a variety of gene mutations, and gene therapy with targeted mutated genes is limited to a certain extent, which still needs to be continuously explored and improved.
  • Androgen therapy: It is effective for bone marrow failure in some patients with FA, but cannot cure FA. It may only be applied to patients waiting for allogeneic hematopoietic stem cell transplantation (HCT) or patients who are unable to carry out HCT. However, attention should be paid to monitoring the occurrence of adverse reactions.
  • Hematopoietic stem cell transplantation: FA can be cured, but the selection of pretreatment scheme during transplantation and post-transplantation rejection, especially the recurrence of solid tumor after transplantation, have affected the development of this treatment.

With the deepening of research on the pathogenesis of FA, great progress has been made in the diagnosis and treatment of patients with FA, but there are still many problems that have not been clarified. Therefore, further research on the pathogenesis of FA is needed in order to find better treatment options.

Does Fanconi anemia need hospitalization?

Patients with Fanconi anemia require hospitalization.

Can Fanconi anemia be cured?

Hematopoietic stem cell transplantation can cure this disease, but this treatment is still immature at present. The selection of pretreatment scheme during transplantation and post-transplantation rejection, especially the recurrence of solid tumor after transplantation, all affect the development of this treatment.


What Should Fanconi Anemia Patients Pay Attention To In Life?

Patients with Fanconi anemia need to get enough sleep, avoid infection, eat well, and be well nourished.

Fanconi anemia needs regular re-examination and relevant indexes such as hematology should be re-examined according to the doctor's advice.

Fanconi anemia affects fertility. Some patients with this disease may have reproductive system agenesis, for example, 50% female patients may have infertility, and pregnant women with FA are prone to complications (eclampsia, premature birth); For male patients, gonadal agenesis, external genital deformity and reduction of sperm quantity are more common, so the disease affects fertility.

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