OBJECTIVE: Pearson bone marrow-pancreas syndrome (PS) is a rare, usually fatal mitochondrial disorder involving the hematopoietic system in early infancy. Due to the diversity of clinical symptoms, the diagnosis can be difficult. The authors describe a boy with severe hypoplastic anemia in whom extensive clinical, biochemical, and morphologic findings led to the diagnosis of PS, and molecular analysis revealed a novel deletion of mitochondrial DNA from nucleotide position 10.371 to 14.607. METHODS: The patient is a 2-year-old boy who presented at age 5 months with hypoplastic macrocytic anemia. His first months of life and the family history were uneventful. Extensive pretransfusion evaluations did not reveal a metabolic, infectious, or hematologic-neoplastic etiology, and he had no evidence of exocrine pancreatic insufficiency. However, a second bone marrow aspirate at age 7 months showed a reduced cell number, vacuolated erythroblasts and myeloblasts, and ringed sideroblasts, so PS was suspected. RESULTS: Additional molecular analysis from the boy's blood leukocytes revealed a deletion of mitochondrial DNA from nucleotide position 10.371 to 14.607, which was absent in his mother's blood cells, consistent with a sporadic mutation as commonly seen in PS. The muscle histology and the respiratory chain enzymes were normal. CONCLUSIONS: Mitochondriopathies should be considered in children with persistent non-neuromuscular symptoms such as unexplained refractory anemia. Due to the often-fatal course of PS, the rapid detection of mitochondrial DNA deletions is imperative for diagnosis and family counseling.
OBJECTIVE: Pearson bone marrow-pancreas syndrome (PS) is a rare, usually fatal mitochondrial disorder involving the hematopoietic system in early infancy. Due to the diversity of clinical symptoms, the diagnosis can be difficult. The authors describe a boy with severe hypoplastic anemia in whom extensive clinical, biochemical, and morphologic findings led to the diagnosis of PS, and molecular analysis revealed a novel deletion of mitochondrial DNA from nucleotide position 10.371 to 14.607. METHODS: The patient is a 2-year-old boy who presented at age 5 months with hypoplastic macrocytic anemia. His first months of life and the family history were uneventful. Extensive pretransfusion evaluations did not reveal a metabolic, infectious, or hematologic-neoplastic etiology, and he had no evidence of exocrine pancreatic insufficiency. However, a second bone marrow aspirate at age 7 months showed a reduced cell number, vacuolated erythroblasts and myeloblasts, and ringed sideroblasts, so PS was suspected. RESULTS: Additional molecular analysis from the boy's blood leukocytes revealed a deletion of mitochondrial DNA from nucleotide position 10.371 to 14.607, which was absent in his mother's blood cells, consistent with a sporadic mutation as commonly seen in PS. The muscle histology and the respiratory chain enzymes were normal. CONCLUSIONS: Mitochondriopathies should be considered in children with persistent non-neuromuscular symptoms such as unexplained refractory anemia. Due to the often-fatal course of PS, the rapid detection of mitochondrial DNA deletions is imperative for diagnosis and family counseling.
Authors: Saskia B Wortmann; Leo A J Kluijtmans; Richard J Rodenburg; Jörn Oliver Sass; Jessica Nouws; Edwin P van Kaauwen; Tjitske Kleefstra; Lisbeth Tranebjaerg; Maaike C de Vries; Pirjo Isohanni; Katharina Walter; Fowzan S Alkuraya; Izelle Smuts; Carolus J Reinecke; Francois H van der Westhuizen; David Thorburn; Jan A M Smeitink; Eva Morava; Ron A Wevers Journal: J Inherit Metab Dis Date: 2013-01-25 Impact factor: 4.982