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Approximately 200 cases have been reported in the literature. Both males and females are affected. The prevalence of Pearson syndrome is approximately 1/1,000,000.

Most patients present with sideroblastic anemia in infancy. Additional symptoms comprise failure to thrive, neurological (hypotonia, speech delay, muscular hypertrophy) and gastrointestinal (vomiting, chronic diarrhea and feeding difficulties) symptoms. All organs can be affected and various complications develop during the course, which are generally irreversible. Hepatic dysfunction (hepatomegaly, splenomegaly), exocrine pancreatic insufficiency and renal tubulopathy are common early complications, while ophthalmological complications (such as retinitis pigmentosa and cataract) and cardiac conduction defects usually occur at a later stage of the disease. Patients often develop multiple endocrine disorders. Interestingly, hematological recovery spontaneously occurs in a majority of patients at 1-3 years of age, while some patients develop myeloid neoplasms in early childhood. Patients who survive early infancy can demonstrate a Kearns-Sayre syndrome-like phenotype.

Pearson syndrome is caused by large-scale mitochondrial DNA (mtDNA) deletions which lead to a deficiency in mitochondrial respiratory chain function. Heteroplasmy (mixture of both wild-type and deleted mtDNA in the same cell) can be observed in patients and explains the high variability in clinical expression, both between patients and between the various organs of an affected subject. Cellular dysfunction appears only if the level of heteroplasmy exceeds a certain critical threshold.

The diagnosis of Pearson syndrome is usually suspected based on the typical bone marrow cytology with vacuolization in erythroid and myeloid precursors. Iron staining reveals ring-sideroblasts in 70-85% of patients. The diagnosis should be confirmed by genetic testing (detection of large-scale mtDNA deletion).

Patients with Pearson syndrome can be misdiagnosed as Diamond-Blackfan anemia, a congenital hypogenerative anemia that presents in infancy.

Most cases are sporadic. Although deleted mtDNA can be maternally inherited, the unpredictable heteroplasmy status in a child makes genetic counseling challenging.

Similar to the majority of patients with primary mitochondrial diseases, there is no curative therapy for children with Pearson syndrome. Therapy is largely supportive and includes blood transfusions, treatment of infections, prevention of metabolic decompensations, and therapy for various organ complications such as pancreatic insufficiency and endocrine disorders. Most patients receive supplements such as coenzyme Q10, L-carnitine and/or various vitamins, despite limited evidence for efficacy.

Patients with Pearson syndrome have a dismal prognosis. About half of patients die by 4 years of age. Patients who reach 15 years of age are rare. The most common cause of death is metabolic decompensation with lactic acidosis. Patients who survive early infancy typically undergo phenotypic change: hematological manifestations spontaneously resolve, whereas neurological and myopathic signs either appear or worsen. Some patients develop Kearns-Sayre syndrome (KSS) with ophthalmoplegia, ataxia, pigmentary retinitis, conduction defects and myopathy.

Last update: May 2023 - Expert reviewer(s): Pr Sarah GRÜNERT | MetabERN* - Dr Ayami YOSHIMI | PaedCan-ERN*

* European Reference Network