Fanconi anemia

Fanconi anemia

Updated: 7/9/2024

© Jun Wang, MD, PhD

 

General features

  • Most common form of inherited aplastic anemia
  • Autosomal recessive
  • Approximately 25% of aplastic anemia
  • Associated with cytopenias, predisposition to malignancy, and congenital and developmental abnormalities

Major causes

  • Mutations in one of over 22 genes, FANCA to FANCW
  • Most commonly mutated genes: FANCA, FANCC, and FANDG

Key pathogenesis

  • Biallelic mutations of FANCA, FANCC, and FANCG most common
  • Heterozygous FA mutations considered asymptomatic carriers, except

o   FANCB (X-linked recessive)

o   FANCR (autosomal dominant)

o   FANCS and FANCD1 (AKA BRCA1 and BRCA2, respectively)

  • Defects in DNA interstrand crosslink repair
  • Cells highly vulnerable to endogenous injuries, such as ROS
  • Anemia associated with selective destruction of CD34+ stem cells

Key clinical findings

  • Early onset with concurrent birth defects
  • Cytopenia/bone marrow failure

o   Macrocytic anemia

o   Thrombocytopenia: bleeding

o   Neutropenia infections

o   Pancytopenia

Key Laboratory findings

  • Blood: Cytopenia including macrocytic anemia, thrombocytopenia, leukopenia or pancytopenia
  • Bone marrow

o   Hypocellular

o   Loss of myeloid and erythroid precursors

o   Loss of megakaryocytes

o   Relative lymphocytosis

o   Severe cases with fatty changes

o   Features of MDS or leukemia

Diagnosis

  • Based on findings of chromosome breaks, or FA mutations
  • Indications for screening

o   Persistent moderate to severe cytopenias: >2 weeks of moderate or severe cytopenias in ≥2 lineages with severely hypocellular bone marrow, without any known cause

o   Characteristic physical findings: ≥3 of the following: vertebral anomalies, anal atresia, congenital heart disease, tracheoesophageal fistula, esophageal atresia, renal anomalies, limb anomalies, and hydrocephalus) or multiple malformations, such as short stature, cafĂ©-au-lait spots, thumb/radial ray abnormalities, or hypospadias that are strongly associated with FA

o   Relative with FA patients

o   Unexplained cytopenias associated with characteristic congenital abnormalities

o   Individuals ≤40 years with MDS, AML, or certain cytogenetic abnormalities

o   Squamous cell cancer (SCC) of the head, neck, or anorectal region with no known attributable exposure

o   Patients who had severe toxicity with chemotherapy or radiation therapy 

Management

  • Supportive: transfusion
  • Hematopoietic stem cell transplantation
  • MDS or leukemia may be treated or prevented by hematopoietic stem cell transplantation
  • Androgens if stem cell transplantation not an option
  • Treatments of concurrent defects or disorders

Prognosis

  • Death due to bleeding or infection
  • Incidence of solid tumor rising due to improvement of survival

 

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Contents

Pathology notes Jun Wang, MD, PhD 1. General information Frequently discussed syndromes Terms of dermatology Terms of hematology 2. Primary immunodeficiency disorders 3. Hemodynamic abnormalities Shock Thrombosis and embolism Bleeding disorders 4.  Benign blood cell disorders Anemia Benign white cell disorders 5. Hematopoietic neoplasms Lymphoid neoplasms Myeloid neoplasms Histiocytic neoplasms: Langerhans cell histiocytosis 6. Cardiovascular system Pulmonary hypertension Cardiovascular system tumors 7. Respiratory tract tumors 8. Gastrointestinal tract Congenital disorders Infectious gastroenteritis Oral cavity Esophagus Stomach Intestinal tumors Salivary glands Exocrine pancreas and gallbladder 9. Urinary system Kidney masses Lower urinary tract 10. Male reproductive system 11. Female genital tract 12. Breast 13. Endocrine organs Pituitary gland Adrenal gland Thyroid gland Parathyroid gland Endocrine pancreas M
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Anemia

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Practice questions Anemia I

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Practice questions Anemia I © Jun Wang, MD, PhD   Abbreviations: Hb: hemoglobin HCT: hematocrit MCV: Mean Corpuscular Volume MCHC: Mean Corpuscular Hemoglobin RDW: Red Cell Distribution Width TIBC: total iron binding capacity   1. Use this case for the next three questions . A 25-year-old woman is brought to the emergency department 2 hours after being involved in a motor vehicle accident. She is conscious but feels dizziness and weakness.   Her blood pressure is 90/60 mmHg, and her heart rate is 120 beats per minute. Physical examination reveals pale skin and mucosa and a 15 cm laceration on her left thigh with significant bleeding. What are most likely the CBC and TIBC results? A. Low Hb, low HCT, high MCV, high RDW, high TIBC B. Low Hb, low HCT, slightly low MCV, normal RDW, normal TIBC C. Low Hb, low HCT, slightly high MCV, normal RDW, normal TIBC D. Normal Hb, normal HCT, normal MCV, normal
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