Pearson syndrome

Other Names: Sideroblastic anemia with marrow cell vacuolization and exocrine pancreatic dysfunction (formerly); Pearson's marrow/pancreas syndrome; Pearson's syndrome; Pearson marrow-pancreas syndrome

Pearson syndrome affects many parts of the body but especially the bone marrow and the pancreas. Pearson syndrome affects the cells in the bone marrow (hematopoietic stem cells) that produce red blood cells, white blood cells, and platelets.

Epidemiology

Pearson marrow-pancreas syndrome is a rare condition; its prevalence is unknown.

Cause

Pearson marrow-pancreas syndrome is caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA (mtDNA). This type of DNA contains many genes essential for normal mitochondrial function. Pearson marrow-pancreas syndrome is caused by single, large deletions of mtDNA, which can range from 1,000 to 10,000 DNA building blocks (nucleotides). The most common deletion, which occurs in about 20 percent of affected individuals, removes 4,997 nucleotides.

The mtDNA deletions involved in Pearson marrow-pancreas syndrome result in the loss of genes that provide instructions for proteins involved in oxidative phosphorylation. These deletions impair oxidative phosphorylation and decrease the energy available to cells. It is not clear how loss of mtDNA leads to the specific signs and symptoms of Pearson marrow-pancreas syndrome, although the features of the condition are likely related to a lack of cellular energy.

Inheritance

Pearson marrow-pancreas syndrome is generally not inherited but arises from new (de novo) mutations that likely occur in early embryonic development.

Signs and symptoms

Pearson syndrome affects the cells in the bone marrow (hematopoietic stem cells) that produce red blood cells, white blood cells, and platelets. When there aren't enough healthy red blood cells (anemia), the body becomes very weak, the child's skin is pale, and the child is very tired (fatigued). Children with Pearson syndrome are anemic because the iron which should be in the hemoglobin, ends up instead in the mitochondria. Without hemoglobin, these cells (ringed sideroblast) cannot carry oxygen.

When a person has too few white blood cells (neutropenia), it is more difficult for the body to fight infection, which can cause frequent colds and sickness.

When a person doesn't have enough platelets (thrombocytopenia), the blood does not clot as well, which can cause a child to take a long time to stop bleeding. Some children with Pearson syndrome have problems with all three blood cell types, but other children may not.

Pearson syndrome may also affect the pancreas, which is a gland found in our abdomen or belly. The pancreas is responsible for making special proteins called digestive enzymes which break down the food we eat. The pancreas also produces hormones (insulin and glucagon) which help control the sugar levels in our blood. A child with Pearson syndrome can have symptoms such as frequent diarrhea and stomach pain, and it may be difficult for them to gain weight. They may also have diabetes if the pancreas doesn't produce enough insulin. Some children with Person syndrome may also have problems with their liver, kidneys, heart, eyes, ears, and/or brain. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal hemoglobin
• Abnormality of skin pigmentation(Abnormal pigmentation)
• Anemia(Low number of red blood cells or hemoglobin)
• Delayed skeletal maturation(Delayed bone maturation)
• Exocrine pancreatic insufficiency(Inability to properly digest food due to lack of pancreatic digestive enzymes)
• Failure to thrive(Faltering weight)
• Intrauterine growth retardation(Prenatal growth deficiency)
• Lactic acidosis(Increased lactate in body)
• Malabsorption(Intestinal malabsorption)
• Metabolic acidosis
• Muscular hypotonia(Low or weak muscle tone)
• Pancreatic fibrosis
• Reduced bone mineral density(Low solidness and mass of the bones)
• Type I diabetes mellitus(Type 1 diabetes)

Diagnosis

Many tests may be needed to diagnose Pearson syndrome, including a bone marrow biopsy to look for signs of sideroblastic anemia or a bowel movement sample to measure the amount of fat in the stool. The doctors may also test the urine to check for certain organic acids which would be a sign of metabolic acidosis. Finally, genetic testing for changes or mutations in mitochondrial DNA would confirm the diagnosis. The results of the genetic test may be especially important. Although Pearson syndrome is usually caused by deletions of mitochondrial DNA, duplication of mitochondrial DNA can also cause symptoms of Pearson syndrome. Whether the condition is caused by a deletion or duplication of DNA may affect how the disease progresses.

Treatment

Unfortunately, there is no cure for Pearson syndrome, and the goal of treatment is to decrease the seriousness of symptoms so the child can live as healthy and as long of a life as possible. Children affected by Pearson syndrome may require frequent blood transfusions to help supply the body with healthy red blood cells. Pancreatic enzyme replacement may also help to replace the missing enzymes needed to digest food, or insulin injections may be necessary to treat diabetes.

It is important that children affected by Pearson syndrome avoid other people who are sick with viral or bacterial infections, as these children cannot fight off illnesses as well as other children can. Other treatments depend on the specific symptoms presented by each person with Pearson syndrome. It may be necessary to see specialists for the liver, kidneys, heart, and pancreas. Physical or occupational therapy may be helpful, especially in children who live past infancy. Unfortunately, a stem cell transplant has not been shown to be helpful in curing a disease that affects many systems in the body like Pearson syndrome does. It is, however, important to ask your doctors about any new or promising treatments for Pearson syndrome.

Prognosis

Unfortunately, the prognosis for Pearson syndrome is not good. Pearson syndrome usually causes a baby to die while still an infant. If a child lives past infancy, he or she may begin to have fewer symptoms of Pearson syndrome, and the symptoms may be less severe. Many of the children who survive past age 4 go on to have symptoms of a different disease called Kearns-Sayre syndrome. This disease is more likely to affect the brain, spinal cord, and nerves. Symptoms of Kearns-Sayre syndrome include weak eye muscles and difficulty coordinating movements. It is important for a child with Pearson syndrome to be monitored by their doctors for any changes in symptoms as they get older.

NIH genetic and rare disease info

• NIH info on Pearson syndrome

Pearson syndrome is a rare disease.

Pearson syndrome Resources
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