What are the other Names for this Condition? (Also known as/Synonyms)

• Pearson Syndrome
• PMPS (Pearson Marrow-Pancreas Syndrome)
• Sideroblastic Anemia with Marrow Cell Vacuolization and Exocrine Pancreatic Dysfunction

What is Pearson Marrow-Pancreas Syndrome? (Definition/Background Information)

• Pearson Marrow-Pancreas Syndrome is a very rare disorder wherein there is failure of bone marrow to function well. Organs such as pancreas and liver may also be affected, though many researchers consider it to be mainly a bone marrow disorder
• Bone marrow is the spongy tissue found inside the bones. Normally, it is the main site of blood cell production (hematopoiesis). The blood cells include:
  • Red blood cells (erythrocytes), which transport ‘gases’ such as oxygen
  • White blood cells (leukocytes), important to the immune system
  • Megakaryocytes, which fragment to form platelets. Platelets clot blood and recruit collagen-producing cells (fibroblasts) to the scene of an injury
• These diverse cells develop from myeloid stem cells (blasts) inside the bone marrow. This process is mediated by different signals that steer the growth and division of the blasts, down different pathways (lineages)
• The different blood cells can thus be considered “cousins” of each other. This is because they share a common ancestral stem cell, though they have diverged down separate lineages
• The signs and symptoms due to poorly-functioning bone marrow include:
  • Shortage of red blood cells (anemia) leading fatigue and tiredness
  • Low numbers of white blood cells (neutropenia) leading to frequent infections
  • Low number of platelets (thrombocytopenia) leading to frequent bleeding

Who gets Pearson Marrow-Pancreas Syndrome? (Age and Sex Distribution)

• Pearson Marrow-Pancreas Syndrome is a very infrequent condition that affects infants and children. The signs and symptoms of this syndrome usually begin at birth
• Both males and females can be affected
• The condition can occur worldwide; individuals of all racial and ethnic background may be affected

What are the Risk Factors for Pearson Marrow-Pancreas Syndrome? (Predisposing Factors)

• The specific risk factors for Pearson Marrow-Pancreas Syndrome are unknown or unidentified; this condition is not associated with any genetic syndromes

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your health care provider.

What are the Causes of Pearson Marrow-Pancreas Syndrome? (Etiology)

• The exact cause of Pearson Marrow-Pancreas Syndrome development is unknown
• Research scientists believe that the cause of the condition is mostly due to genetic mutations that results in defects in mitochondria function
• The condition is not an inherited disorder. It is caused by sporadic (random) mutations during fetal development

What are the Signs and Symptoms of Pearson Marrow-Pancreas Syndrome?

Individuals with Pearson Marrow-Pancreas Syndrome can vary in the severity of symptoms. On the basis of which specific blood cell type is affected, the signs and symptoms can be:

• Due to decrease in the number of red blood cells (anemia):
  • Fatigue (increased desire to sleep), weakness
  • Dizziness, light-headedness
  • Shortness of breath, difficulty breathing
  • Pale skin
  • Chest pain
  • Headache
• Due to decrease in the number of white blood cells (leukopenia):
  • Frequent infections or,
  • Life-threatening infections
• Due to decrease in the number of platelets (thrombocytopenia):
  • Easy bruising with minimal trauma
  • Bleeding of the gums
  • Nosebleeds
  • Increased menstrual blood flow
  • Spontaneous life-threatening internal bleeds
  • Abdominal pain, back pain
  • Loss of appetite

Pancreatic fibrosis can lead to signs and symptoms such as:

• Weight loss
• Indigestion
• Yellowing of skin (jaundice)
• Nausea and vomiting
• Dark-colored urine
• Fatigue (getting tired easily)

Individuals with Pearson Marrow-Pancreas Syndrome may have malabsorption due to reduced ability to absorb nutrients from the intestine. Signs and symptoms of malabsorption include the following:

• Feeling of bloated abdomen (especially the intestines), passing gas regularly
• Irregularly, stomach/abdominal pain with cramps. The cramps may be mild, or in some cases severe and painful
• Vomiting, nausea
• Constipation or diarrhea
• Weight loss

The signs and symptoms of Pearson Marrow-Pancreas Syndrome are usually severe.

How is Pearson Marrow-Pancreas Syndrome Diagnosed?

The diagnosis of Pearson Marrow-Pancreas Syndrome may include:

• A thorough physical examination and a complete medical history
• Complete blood count with differential (CBC): Whenever blood test results indicate a decrease in all 3 cell types (RBCs, WBCs, and platelets) and pancreatic function abnormalities, Pearson Marrow-Pancreas Syndrome must be highly suspected. Blood analysis may also show increased bleeding time
• Comprehensive metabolic panel (CMP): A group of blood tests done to check the body’s chemical balance and metabolism
• Serum blood tests to check for folate, iron levels, vitamins B12 and D
• Liver function tests
• Blood test to check for serum amylase levels
• Imaging procedures such as:
  • CT, MRI scans of abdomen
  • MR cholangio-pancreatography (MRCP)
  • Endoscopic retrograde cholangio-pancreatography (ERCP)
  • MR angiography (MRA)
  • Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the gastrointestinal tract. The use of esophagoduodenoscopy will bring out the mucosal changes
• Bone marrow biopsy:
  • A bone marrow biopsy may be performed to make a definitive diagnosis of Pearson Marrow-Pancreas Syndrome. It may reveal an absence of the precursor cells that form all the 3 blood cell types. It is also done to rule-out other diseases, such as myelodysplastic syndrome (MDS) and paroxysmal nocturnal hemoglobinuria (PNH), which may be associated with Pearson Marrow-Pancreas Syndrome
  • Bone marrow aspiration and biopsy are usually performed on the pelvic bone. But, it can also be performed on the breast bone (sternum), or a leg bone (below the knee, above the foot).
  • In this procedure, a large hollow needle is inserted through the skin, muscle, tissue and finally into the bone. The doctor uses twisting hand motion to penetrate the bone and push the needle into the bone marrow cavity. The fluid from the bone marrow is then extracted and the needle withdrawn
  • The extracted fluid/tissue is sent to the lab for examination by a pathologist to make a definitive diagnosis. The pathologist may order special tests as required
• Liver tissue biopsy: A liver biopsy to determine fatty change in liver may be performed and sent to a laboratory for a pathological examination to the pathologist, who examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pearson Marrow-Pancreas Syndrome?

The complications of Pearson Marrow-Pancreas Syndrome include:

• Severe, life-threatening bleeding in the internal organs such as the brain or abdomen
• Severe, life-threatening infections
• Metabolic disorders such as lactic acidosis
• Heart and liver failure
• Diabetes may develop if sufficient numbers of islet cells of pancreas are destroyed by the scarring process
• Severe Anemia
• Severe mineral, vitamin deficiencies causing a host of complications
• In children, severe deficiencies may lead to delayed bone maturation, failure to grow and thrive

How is Pearson Marrow-Pancreas Syndrome Treated?

The treatment of Pearson Marrow-Pancreas Syndrome varies depending on the signs and symptoms. It is based on the age and health status (whether mild or severe condition) of the affected individual, and the availability of bone marrow donors.

The initial treatment attempted is to bring about a symptomatic improvement of the individual. The measures may include:

• Packed cell volume (blood transfusion) to increase the count of red blood cells, for relief from anemic symptoms
• Platelet transfusion to counter any active bleeding
• Antibiotics to treat infections
• Giving lot of fluids and electrolytes, to make up for the lost body fluids and nutrients
• Replacement of deficient folate, iron, vitamin B12, and other vitamins

Long-term treatment options for Pearson Marrow-Pancreas Syndrome may include:

• Allogeneic bone marrow transplant: This is the most preferred treatment in children and young adults. In this type of bone marrow transplantation, chemotherapy or radiation is used to destroy the abnormal bone marrow cells. These are then replaced by normal bone marrow cells from a donor by injecting them intravenously into the patient's body, where they travel to the bone marrow and begin to produce new blood cells. Ideally, the best match is obtained from identical twins, siblings, or close relatives having the closest genetic makeup of the individual. But, most of the times, the donors are not necessarily related and only a basic compatibility is sought
• Peripheral stem cell transplantation: Another, similar procedure known as peripheral stem cell transplantation may also be used. In this method, the donor's blood stream is the source of the stem cells, which are intravenously injected into the patient's blood. However, generally better results are obtained with a bone marrow transplant instead of a peripheral stem cell transplant
• Hematopoietic growth factors: It is used when individuals do not respond to immunosuppressive therapy. The growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), and granulocyte-colony stimulating factor (G-CSF) are injected into the bloodstream, to stimulate the production of blood cells. The procedure may assist in increasing the counts

How can Pearson Marrow-Pancreas Syndrome be Prevented?

Currently, there are no specific methods or guidelines to prevent Pearson Marrow-Pancreas Syndrome.

What is the Prognosis of Pearson Marrow-Pancreas Syndrome? (Outcomes/Resolutions)

• The prognosis for Pearson Marrow-Pancreas Syndrome depends on the severity of signs and symptoms. It also depends on the availability of matched donors, access to tertiary care facilities, the kind of complications arising from bone marrow transplant, and response to therapy
• Individuals, who respond to treatment better, have better prognosis compared to those who do not respond so well to treatment
• In general the prognosis for Pearson Marrow-Pancreas Syndrome is poor. Over half die during infancy or childhood, due to metabolic disorders or liver failure
• If left untreated, Pearson Marrow-Pancreas Syndrome can lead to death

Additional and Relevant Useful Information for Pearson Marrow-Pancreas Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/