Search for a rare disease
Other search option(s)
Pearson syndrome is characterized by refractory sideroblastic anemia, vacuolization of bone marrow precursors and exocrine pancreatic dysfunction.
ORPHA:699Classification level: Disorder
Approximately 60 cases have been described. Both sexes are affected.
Hematological signs begin in infancy, although a few neonatal cases have been described. These signs include macrocytic sideroblastic anemia, sometimes associated with potentially deep neutropenia or thrombocytopenia. The presence of vacuolization in granulous and erythroblastic progenitors, visible on the myelogram, is highly suggestive of the syndrome. Perls coloration reveals the presence of ringed sideroblasts. Besides the hematological deficiency, patients present with fibrotic exocrine pancreatic dysfunction with malabsorption and diarrhea, or a defect in oxidative phosphorylation resulting in lactic academia (sometimes intermittent) and an increased lactate/pyruvate ratio. Other organs can be affected, either simultaneously or during the course of the disease: frequent renal involvement with tubulopathy and aminoaciduria is observed, as well as hepatic involvement with hepatomegalia, cytolysis and cholestasis, endocrine gland disturbances, neuromuscular disorders and, in few cases, cardiac involvement and splenic atrophy. The overall pleiotropic clinical picture is evocative of the ``illegitimate'' association of multiple organ disorders in a single patient.
Physiopathologically, this syndrome is a mitochondrial cytopathy. It is caused by mitochondrial DNA deletions, which constitute a diagnostic criterion. These deletions lead to a deficiency in mitochondrial respiratory chain function. The random distribution of mitochondrial DNA during cell division is responsible for the presence of both normal and mutated DNA in a single cell. This coexistence, named heteroplasmy, explains the high variability in clinical expression observed both between patients and between the various organs of an affected subject. Indeed, pathological manifestations occur when some level of mutated DNA has accumulated in a given tissue.
Although maternal transmission has been described, Pearson syndrome is typically sporadic.
Management and treatment
There is no specific treatment of Pearson syndrome. Management is symptomatic and includes treatment of infectious episodes and of metabolic accidents, transfusion in case of deep anemia (sometimes associated with erythropoietin therapy), uptake of pancreatic extracts and management of endocrine disorders.
Death often occurs before the age of three years, due to septic risks, metabolic crisis with lactic acidosis or hepatocellular failure. Patients who survive early infancy typically undergo phenotypic evolution: hematological manifestations spontaneously resolve, whereas neurological and myopathic signs either appear or worsen. Some patients develop typical Kearns-Sayre syndrome (KSS) with ophthalmoplegia, ataxia, pigmentary retinitis, conduction defects and myopathy.
Article for general public