Pearson syndrome symptoms, causes and treatments

The Pearson's syndrome it is a disease of the mitochondrial type that affects the whole body, that is, its involvement is multi-system. Its onset occurs in childhood and occurs due to deletion of mitochondrial DNA.

This syndrome was first described in 1979 by Howard Pearson, a pediatrician specializing in hematology. A decade later, the mitochondrial DNA deletions that cause this syndrome were discovered.

This multisystemic disease is caused by an abnormality in oxidative phosphorylation, which is the metabolic process by which energy released by the oxidation of nutrients is used to produce adenosine triphosphate (ATP). The abnormality of this process is due to the duplication of mitochondrial DNA.

Despite being a mitochondrial disease, that is, it is transmitted by the mother, it has been concluded that Pearson's syndrome is usually sporadic. Therefore, there are mitochondrial DNA deletions and they serve as diagnostic criteria, but the random distribution of this type of DNA causes normal cells and others with mutations to converge..

This fact, called heteroplasmy, which occurs when an individual has a mixture of different populations of mitochondria, is the cause of the great variability in the clinical expression of the disease.

This term refers to the fact that, despite responding to the same diagnosis, different individuals will show different symptoms, as well as different levels of affectation.

Article index

• 1 What is its prevalence?
• 2 Symptoms
  • 2.1 Refractory sideroblastic anemia
  • 2.2 Vacuolization of bone marrow precursors
  • 2.3 Exocrine dysfunction of the pancreas
• 3 Diagnosis
• 4 Treatment
• 5 Forecast
• 6 Bibliography

What is its prevalence?

Being a rare disease, it affects a minority of the population. According to the European portal for Rare Diseases, Orphanet, Pearson's syndrome has a prevalence of <1 / 1.000.000.

In addition, he adds that there are no more than 60 cases described. The type of inheritance that Pearson syndrome transmits, as it is not related to sex, affects both boys and girls in the same way.

Symptoms

The onset of Pearson's syndrome is in the infantile stage and there are few cases described that are neonatal. The first signs are visible during the lactation period and before six months of life.

This syndrome presents a very varied picture, with different conditions. There are three characteristics that any person who suffers from Pearson syndrome presents and they are the following:

Refractory sideroblastic anemia

It is the quintessential symptom of Pearson syndrome and consists of the alteration of the synthesis of hemoglobin in the precursors of the bone marrow. In this way, the so-called ring sideroblasts are produced..

For its treatment, it is convenient to control anemia and, in addition, prevent iron overload.

Sometimes this anemia is associated with profound neutropenia that consists of a decrease in the number of neutrophils (commonly known as leukocytes or white blood cells)..

Also thrombocytopenia; when an abnormal hematological situation occurs and the number of platelets is lower. It occurs due to the destruction of red cell tissue in the bone marrow.

Vacuolization of bone marrow precursors

The cells that are the precursors of the bone marrow, in the case of Pearson syndrome, increase their size considerably.

Exocrine dysfunction of the pancreas

This dysfunction is the inability of the exocrine pancreas to perform digestive functions normally. It is usually caused by a sudden reduction in pancreatic secretion.

It is closely related to poor digestion and, as a consequence, leads to poor absorption of undigested food that often leads to a state of malnutrition.

There is great variability in the expression of Pearson syndrome, due to the fact that the pathogenic cells are together with the normal cells. For a person to present pathological manifestations, they must accumulate a sufficient amount of mutated DNA.

Sometimes and due to the different organs and systems that are affected, Pearson's syndrome is thought to consist of an “incoherent” association of symptoms.

Diagnosis

Usually the diagnosis can be made based on the symptoms observed. However, and as indicated by the Pearson Syndrome Association, it is necessary to carry out different tests and examinations to conclude on the diagnosis of this syndrome..

First, when a mitochondrial syndrome is suspected, a preventive analysis can be carried out to determine the most frequent genetic alterations in mitochondrial DNA..

Another very important test in Pearson syndrome is the muscle biopsy and in the event that different symptoms converge, it is essential. This test consists of the removal of a small sample of muscle tissue to be examined and analyzed. It is a quick and minimally invasive test and it is also not painful.

Neuroradiology is useful in the diagnosis of this syndrome since it offers images of the state of the brain and the existence of any abnormality can be detected. Thanks to laboratory studies, the levels of lactic acid and cerebrospinal fluid will be measured and thus it will be possible to establish if they respond to medium levels or, if there is any type of abnormality.

Last but not least, tests are carried out that analyze the activity of enzymes.

In cases where there are cardiac symptoms or that affect other organs or systems, such as vision, the corresponding tests will be carried out in order to apply the treatment they require. Gastroenterological and nutritional studies can also be carried out to verify that the absorption of nutrients is being carried out correctly..

Treatment

To this day, Pearson's syndrome requires symptomatic treatment. That is, there is no therapy or medication to cure the disease and, therefore, the treatments are aimed at alleviating the symptoms that this syndrome causes in individuals who suffer from it..

For this and, first of all, it is very important to have carried out an exhaustive analysis that yields data on the minor's health status and what their deficiencies are in order to focus the treatment in the most appropriate way. In addition, medical check-ups are necessary to be able to check the evolution and verify that the treatment being used is appropriate..

Normally, treatment will be aimed at alleviating infectious episodes and metabolic problems.

In cases where anemia is severe, blood transfusions will be prescribed. On certain occasions, this treatment will be accompanied by erythropoietin therapy that consists of the application of a hormone that will contribute to the creation of red blood cells, also known as erythrocytes..

Also, if there are any, endocrine disorders or symptoms that affect other organs that have not been mentioned in this section and that I mentioned earlier will be treated, such as the visual system, the heart, etc..

Forecast

Unfortunately, Pearson's syndrome often kills these minors before the age of three. The causes are varied and, among them, are:

• Risk of sepsis which is the body's massive response to an infectious process.
• Metabolic crises with lactic acidosis or hepatocellular failure.

There are no figures that tell us about the survival rate of children affected by this syndrome. But, in the event that these minors survive the symptoms, Pearson's syndrome disappears due to the phenotypic evolution, with the hematological symptoms disappearing spontaneously..

With regard to neurological and myopathic signs, they can increase or disappear. In some cases, Pearson syndrome leads to another mitochondrial disease, Kearns-Sayre syndrome..

Bibliography

1. McShane, M.A. (1991) Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. Department of Neurology, Hospital for Sick Children, Queen Square, London.
2. Kearns-Sayre syndrome. Orphanet (2014). 
3. Pearson's syndrome. Orphanet (2006). 
4. Cánovas, R. de la Prieta, J.J. Alonso, C. Ruiz, T. Pereira, C. Aguirre. Sideroblastic anemia (2001). Department and Chair of Internal Medicine. UPV / EHU. Cruces Hospital. Barakaldo.
5. Martín Hernández, M.T. García Silva, P. Quijada Fraile, A. Martínez de Aragón, A. Cabello, M.Á. Martin. Pearson and Kearns-Sayre syndromes: two multisystemic mitochondrial diseases, due to deletions in mitochondrial DNA (2010).
6. Cammarata-Scalisi, F., López-Gallardo, E., Emperador, S., Ruiz-Pesini, E., Da Silva, G., Camacho, N., Montoya, J. Pearson's syndrome. Report of a case (2011).