An infant with Pearson syndrome: a rare cause of congenital sideroblastic anemia and bone marrow failure

Abstract

A 3-month-old boy presented with decreased appetite, fatigue, and a nosebleed. Initial workup revealed hemoglobin 2.6 g/dL (10.2-12.7), hematocrit 7.7% (30.9-37.9), mean corpuscular volume 104 fL (71.3-82.6), white blood cell count 4200/mL (240 absolute neutrophil count), platelets 50 000/mL (140-400), and reticulocyte count 1.31% (1.55-2.7). Bone marrow revealed hypercellularity with cytoplasmic vacuolization of myeloid and erythroid precursors (panels A-B; original magnification 31000, Wright-Giemsa stain). Iron staining of marrow biopsy revealed numerous ringed sideroblasts (panels C-D; original magnification 31000, Prussian blue stain). DNA was examined by array-based comparative genomic hybridization and revealed a 4.9-kb deletion, m.11027_15950del4923, consistent with mitochondrial DNA deletion syndrome, also known as Pearson syndrome. Fecal elastase was initially normal, but now it is ,15 mg/g (normal .200), consistent with severe pancreatic insufficiency. We have begun pancreatic enzyme replacement. Pearson marrow pancreas syndrome (PMPS) is an exceedingly rare mitochondrial disorder. Therefore, prevalence of PMPS is unknown. Affected children typically present in infancy with a hematologic disturbance consistent with an inherited bone marrow failure syndrome and congenital sideroblastic anemia. Important clues to the diagnosis include cytoplasmic vacuolization of erythroid and myeloid precursors along with ringed sideroblasts on bone marrow evaluation. Another hallmark clinical feature is exocrine pancreatic insufficiency. Currently, there is no cure for this condition. The most common causes of death include overwhelming infection, lactic acidosis, and multiorgan failure. For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

Genotype/phenotype correlations of childhood‐onset congenital sideroblastic anaemia in a European cohort

“…Four syndromic subtypes associated with other clinical features are well characterized; these are XLSA with ataxia (XLSA/A, OMIM number 301310) caused by mutations in the ABCB7 gene, encoding a mitochondrial transporter protein involved in the biogenesis of cytosolic Fe‐S clusters (Bekri et al , ; Pondarre et al , ), and the syndrome comprising mitochondrial myopathy, lactic acidosis and sideroblastic anaemia (MLSA, OMIM number 600462), caused by mutations in the PUS1 and YARS2 genes (Bykhovskaya et al , ). The syndrome of thiamine‐responsive megaloblastic anaemia (TRMA, OMIM number 249270), associated with diabetes and deafness, is caused by mutations in the high‐affinity thiamine transporter SLC19A2 (Neufeld et al , ; Bergmann et al , ), while PMPS is associated with large‐scale mitochondrial DNA (mtDNA) deletions, rearrangements or duplications (Pearson et al , ; Rötig et al , ; Falcon & Howard, ). Thanks to next generation sequencing (NGS) and whole exome sequencing (WES), new genes involved in CSA have been identified.…”

Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures

“…Even though both siblings described here did not have hematological features and chromosome breakage studies consistent with Fanconi anemia, other hematological disorders such as sideroblastic anemia have been well described in multisystemic mitochondrial disorders such as Pearson syndrome, MLASA syndrome (mitochondrial myopathy, lactic acidosis, and SA) and complex I deficiency associated with a hemizygous change in NDUFB11 (Falcon & Howard, ; Lichtenstein et al, ; Riley et al, ; Tesarova et al, ). However, it was not until recently that defective oxidative metabolism and mitochondrial localization along with spontaneous mitochondrial fragmentation have been described in Fanconi anemia cells (Bottega et al, ; Cappelli et al, ; Pagano, Shyamsunder, Verma, & Lyakhovich, ).…”

Case Report: Clinical and Genetic Characteristics of Pearson Syndrome in a Chinese Boy and 139 Patients

“…Some children develop neutropenia and/or thrombocytopenia during the course of the disease. Pancytopenia was reported as an initial symptom in some cases ( Falcon and Howard, 2017 ; Tadiotto et al, 2018 ). In this case, the patient’s initial presentation was an episode of moderate anemia.…”