Clinical and Morphological Bone Marrow Characteristics of Pearson Syndrome: About Three Consecutive Cases and Review of the Literature

Pearson syndrome (PS) is a rare and fatal multisystem disorder caused by a mitochondrial DNA (mtDNA) deletion. Most patients develop refractory anemia in early infancy, rapidly followed by multiple complications such as failure to thrive, muscle hypotonia, pancreatic insufficiency, and renal tubulopathy. Although the definitive diagnosis is established by mtDNA sequencing, bone marrow (BM) cytology is a cornerstone of diagnosis, typically revealing precursor vacuolization and ring sideroblasts. We report here three cases of patients with PS encountered in our institution and summarize the clinical and hematological features of PS through a systematic review of the literature. The first symptoms mostly appear during the first month of life and rarely after 18 months. Hyporegenerative anemia, a hallmark of the disease, is the most common initial symptom, followed at a distance by neutropenia and thrombocytopenia. Gastrointestinal and metabolic symptoms such as failure to thrive and lactic acidosis are the most frequent non-hematological symptoms, even in the rare cases without hyporegenerative anemia. Vacuolization of BM precursors, observed in the vast majority of PS patient BMAs, is not influenced by the patient's age at sampling. Ring sideroblasts, the other feature of PS BMAs, are less frequent than progenitor vacuolization but increase significantly after 6 months of age. These abnormalities are just as common in patients with or without hematological symptoms, suggesting that BMA should be performed in all suspected PS cases, despite the absence of anemia. PS is a multisystem disorder requiring early diagnosis and a coordinate multidisciplinary management, involving clinicians and clinical biologists.