Inherited bone marrow failure syndromes

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at November 1, 2016
StartDiseasesInherited bone marrow failure syndromes

Bone marrow failure syndromes represent a group of diseases that share the common underlying feature of some failure of the bone marrow to produce red blood cells, white blood cells, or platelets. The bone marrow failure syndromes may be acquired (as a result of chemotherapy for cancer or as a result of an autoimmune response), or inherited (representing a group of related conditions, usually referred to as the inherited bone marrow failure syndromes).


Definition & Facts

Inherited bone marrow syndromes are a class of diseases in which the disease may be detected relatively soon after birth or later in life when symptoms occur that leads to the diagnosis of a condition that is known to be hereditary or has a tendency to occur in families.

The occurrence rates of inherited bone marrow failure syndromes are poorly understood due to the variable age at when symptoms can first appear. An estimate of 35,000 to 55,000 new cases per year is usually given for the United States.

Symptoms & Complaints

The presenting symptoms of the inherited bone marrow failure syndromes can vary considerably depending on both the type of blood cell affected and the rapidity with which symptoms develop. Anemia usually develops slowly and may be near the life-threatening stage before symptoms prompt a visit to a physician.

Likewise, the increasing susceptibility to infection and/or the slow recovery from minor infections may have been present for months before a problem with white blood cell production is diagnosed. On the other hand, the blood clotting disorders resulting from decreased platelet production usually appear as bruising after only minor contacts or as blood in the urine or as tar-colored stool.

In the case of the non-hereditary types of bone marrow failure, the cause is usually more apparent and can include exposure to environmental toxicants such as lead (lead poisoning) and other heavy metals, organic toxins, chemotherapy, and neoplasms that have metastasized (spread) from other organs.


The inherited bone marrow failure syndromes represent a set of relatively rare subset of hematologic (blood-related) conditions that are not well understood. Some of these conditions may not become apparent until later in life. Many inherited bone marrow syndromes are much more common in certain ethnic groups but there are cases of these diseases that occur in other, diverse groups.

As an example, Fanconi anemia is seen predominately in those of Ashkenazi Jewish ancestry but there are confirmed cases that occur among black South Africans and in the Roma populations of Spain. Several abnormal chromosomes can contribute to the disease itself, and genetic mutations may be triggered by exposure to some environmental toxicant or even medications. Although research in these areas has produced some recent advances in understanding these conditions, much work remains in genetic research before significant progress can be expected.

Diagnosis & Tests

The inherited bone marrow failure syndromes can be very difficult to diagnose, even by hematologists (specialists in the treatment of blood disorders), oncologists (cancer specialists), and immunologists (specialists who treat disorders of the body’s immune system). Since many of these conditions first appear in early to mid-childhood, they can mimic other, more benign conditions such as mononucleosis.

The diagnostic workup of the inherited bone marrow failure begins with a detailed medical history that includes information on the health of the parents, siblings, and first degree relatives. Often, a medical geneticist will develop a genetic pedigree to reveal the presence of a possibly unappreciated inheritance patterns.

An exhaustive physical examination is conducted with attention to physical signs that might have gone unnoticed or were misinterpreted. Small hemorrhages called petechia, which appear as small red to reddish-purple spots, are usually seen on the inner surfaces of the eyelids or in the inside of the lips and cheeks may go unnoticed except by a trained health care provider. On completion of the medical history and physical exam, laboratory tests such as blood tests and bone marrow tests (including bone marrow biopsy) may be conducted during the diagnostic process.

Treatment & Therapy

Treatment of inherited bone marrow syndromes is directed at treating symptoms. If an anemia is present, it will probably be treated with blood transfusions and medications that stimulate red blood cell production or if platelet production is decreased it may respond to platelet-rich blood and plasma products. If the clinical situation is one of overproduction of abnormal or immature cells, such as some of the leukemias, chemotherapy may help to suppress abnormal blood cell production.

Although it is usually considered a last resort, bone marrow transplants from an obviously healthy donor may be considered even though long-term survival after the procedure remains disappointing.

Prevention & Prophylaxis

The bone marrow failure syndromes, whether inherited or acquired, remain some of the more difficult medical conditions to treat simply because they are inherited or they are poorly understood. Due to the continued absence of an effective form of gene replacement technology it does not seem possible that any means of prevention and prophylaxis, other than birth control involving an affected parent, will be available in the immediate or foreseeable future.