He Pearson's syndrome Is one of those known as rare diseases, due to its low prevalence. It consists of a mitochondrial disease that affects the whole body, ie its involvement is multi-system. Its onset occurs in infancy and occurs due to mitochondrial DNA deletion.
This syndrome was first described in 1979 by Howard Pearson, a pediatrician who specializes in hematology. A decade later, the mitochondrial DNA deletions that caused this syndrome were discovered.
Causes of Pearson's syndrome
This multisystem 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 the Adenosine triphosphate (ATP) . The abnormality of this process is due to the duplication of the Mitochondrial DNA .
Despite being a mitochondrial disease, that is, transmitted by the mother, it has been concluded that Pearson syndrome is usually sporadic. Therefore, mitochondrial DNA deletions exist and serve as diagnostic criteria, but the random distribution of this type of DNA causes normal and other mutations to converge.
This fact, called Heteroplasmy , Which occurs when an individual presents a mixture of populations other than mitochondria, is responsible for 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 symptomatology, as well as different levels of affectation.
What is its prevalence?
Being a rare disease, it affects a minority of the population. According to the European Rare Disease Portal, Orphanet, Pearson's syndrome has a prevalence of
In addition, there are no more than 60 cases described. The inheritance type transmitted by Pearson syndrome, because it is not related to sex, affects both boys and girls alike.
What are your symptoms?
The onset of Pearson's syndrome is in the infantile stage and there are few described cases that are of neonates. The first signs are visible during the Breastfeeding period And before the six months of life.
This syndrome presents a very varied picture, with different affections. There are three characteristics that are presented by any person suffering from Pearson syndrome and are as follows:
Refractory sideroblastic anemia
It is the symptom par excellence of Pearson's 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 the anemia and, in addition, to prevent the iron overload.
Occasionally, this anemia is associated with Neutropenia Which consists of a decrease in the number of neutrophils (commonly known as leukocytes or white blood cells).
Also of Thrombocytopenia ; When an abnormal hematological situation occurs and the number of platelets is lower. It occurs due to the destruction of erythrocytic 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's syndrome, increase in size in a considerable way.
Exocrine dysfunction of the pancreas
This dysfunction is the inability of the exocrine pancreas to perform digestive functions in the normal way. It usually occurs by a sudden reduction of pancreatic secretion. It is closely related to poor digestion and, as a consequence, leads to malabsorption of the undigested food that is usually triggered in a state of malnutrition.
There is great variability in the expression of Pearson's syndrome, because pathogenic cells are along with normal ones. For a person to present pathological manifestations, he must accumulate a sufficient amount of mutated DNA. Occasionally and because of the different organs and systems that are affected, Pearson's syndrome is thought to consist of an"incoherent"association of symptoms.
In a publication of the Hospital Universitario Doce de Octubre in Madrid, which consisted of a study of three cases of Pearson's syndrome, they reveal that other symptoms, which tend to occur later, are ocular, endocrine, cardiac and neurological conditions. Regarding cardiac conditions, some patients required the implantation of pacemakers.
To a lesser extent, there are patients diagnosed with Pearson Syndrome who have brain and / or brain stem abnormalities that are visible through the magnetic resonance .
In addition, some of them present hyperlactatorraquia, also known as hypoglucorrhaphy that supposes the decrease of glucose levels in the cerebrospinal fluid. Also, hyperproteinorraquia, increase of the proteins in the cerebrospinal liquid and the decrease of the folic acid in this liquid are common.
How can Pearson Syndrome be diagnosed?
Usually the diagnosis can be made based on the observed symptoms. However, as indicated by the Pearson Syndrome Association, it is necessary to perform different tests and exams to conclude in the diagnosis of this syndrome.
In the first place, when a mitochondrial syndrome is suspected, a preventive analysis can be performed to determine the most frequent genetic alterations in mitochondrial DNA.
Another very important test in Pearson Syndrome is the Muscle biopsy And in the case where different symptoms converge, it is essential. This test involves the removal of a small sample of muscle tissue to be examined and analyzed. It is a quick and non-invasive test and is not painful.
The Neuroradiology Is useful in the diagnosis of this syndrome since it offers images of the state of the brain And the existence of any anomaly can be detected. Thanks to laboratory studies, the levels of lactic acid and cerebrospinal fluid will be measured and thus can be established if they respond to medium levels or, if there is any abnormality.
Last but not least, tests are performed that analyze the activity of the enzymes.
In cases where there are cardiac symptoms or that affect other organs or systems, such as vision, the corresponding tests will be performed in order to apply the treatment they require. Gastroenterological and nutritional studies can also be performed to verify that nutrient absorption is being performed correctly.
Treatment
To date, 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.
To do this, and in the first place, it is very important to have carried out an exhaustive analysis that provides data about the child's health status and what are their shortcomings in order to be able to focus treatment in the most appropriate way. In addition, medical checks are necessary to be able to check the progress and verify that the treatment that is being used is appropriate.
Normally, the treatment will be aimed at alleviating infectious episodes and metabolic problems.
In cases where the anemia Is serious, blood transfusions will be prescribed. In 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 not mentioned in this section and mentioned above, such as the visual system, the heart, etc., will be treated.
It is mortal?
Unfortunately, Pearson's syndrome usually ends the life of these children before the age of three. The causes are varied and, among them, they 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 to tell us about the survival rate of children affected by this syndrome. However, if these children survive the symptomatology, Pearson's syndrome disappears due to phenotypic evolution, and the hematological symptomatology disappears spontaneously.
With regard to neurological and myopathic signs may increase or disappear. In some cases, Pearson's syndrome results in another mitochondrial disease that is the Kearns-Sayre syndrome .
What is Kearns-Sayre Syndrome?
This syndrome, also of the mitochondrial type, is characterized by progressive external ophthalmoplegia (progressive weakness of the ocular muscles and elevators of the eyelid), retinitis pigmentosa (group of degenerative ocular diseases) and its onset occurs before the 20 years of age. Some additional common traits include deafness, Cerebellar ataxia And heart block.
Prevalence figures provided by Orphanet estimate that Kearns-Sayre syndrome affects one person in every 125,000.
Usually, the disease occurs in children with the following symptoms: ptosis (total or partial detachment of an organ), pigmentary retinopathy and progressive external ophthalmoplegia. Other symptoms then follow depending on the distribution of the molecular abnormality, as in Pearson's syndrome.
Other symptoms associated with this syndrome are bilateral sensorineural deafness, cardiac affections, Central Nervous System (Cerebellar ataxia, dysarthria, bilateral facial weakness, intellectual deficit), skeletal muscle myopathy, intestinal and endocrine disorders (delayed puberty, hypoparathyroidism, diabetes) and renal failure. The progression of the disease is slow and can last for decades. During these years, new symptoms may appear or worsen those already present.
Kearns-Sayre syndrome is also caused by deletions of mitochondrial DNA fragments, affecting the Oxidative phosphorylation . There are exceptional cases of this syndrome that occur without deletion of mitochondrial DNA and are as a consequence of point mutations located therein.
The diagnosis is usually made based on the manifestations and, subsequently, the tests performed to confirm it. The tests are usually the same as in the case of Pearson's syndrome. Normally the diagnosis is not made in the prenatal stage.
Most cases of this syndrome occur sporadically. Deletions of mitochondrial DNA are transmitted from one generation to another, in an exceptional manner. It is estimated that less than 4% of women transmit their offspring to mitochondrial DNA deletion. In the case of men, they do not transmit it.
In the same way, the treatment of this syndrome tries to alleviate the provoked symptoms. Regular check-ups of a heart specialist are recommended. In cases where cardiac blockades occur, they will require implantation of the pacemaker or a device that defibrillates to improve the quality of life Of these patients.
Patients suffering from deafness may wear hearing aids. In addition, the supplement Coenzyme Q10 Has proved to be beneficial in some cases. In the case of ophthalmologic manifestations, they can be treated surgically, although the risk of recurrence, as well as possible ocular complications is high.
The prognosis of the person suffering from Kearns-Sayre syndrome will depend on the organs that are affected and the degree of affectation in each of them. This fact is closely related to the proportion of affected and healthy mitochondrial DNA that is located in each of them.
In a large number of cases, the life expectancy of people suffering from this syndrome can be normal if they receive the appropriate medical care, following the treatment and guidelines prescribed by health professionals.
Bibliography
- 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.
- Kearns-Sayre syndrome. Orphanet (2014).
- Pearson's syndrome. Orphanet (2006).
- Cánovas, R. de la Prieta, J.J. Alonso, C. Ruiz, T. Pereira, C. Aguirre. Sideroblastic anemias (2001). Service and Chair of Internal Medicine. UPV / EHU. Hospital of Cruces. Barakaldo.
- Martín Hernández, M.T. García Silva, P. Quijada Fraile, A. Martínez de Aragón, A. Cabello, M.Á. Martin. Pearson and Kearns-Sayre syndromes: two multisystem mitochondrial diseases, due to mitochondrial DNA deletions (2010).
- Cammarata-Scalisi, F., López-Gallardo, E., Emperador, S., Ruiz-Pesini, E., Da Silva, G., Camacho, N., Montoya, J. Pearson's syndrome. Report a case (2011).