title: Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal haemoglobin caused by deletion and duplication of mitochondrial DNA.
abstract: We report a patient with a clinical picture consisting of small birth weight, connatal hypoplastic anaemia, vacuolised bone marrow precursors, failure to thrive, and, subsequently, by insulin-dependent diabetes, renal Fanconi syndrome, lactic acidosis, complex organic aciduria, and elevation of haemoglobin F and of adenosine deaminase activity. The clinical course was progressive and death occurred at age 19 months. A high proportion of mitochondrial (mt) DNA molecules with a deletion of nucleotides 9238 to 15575 were identified in several tissues; about half of the shortened mtDNA molecules were concatenated to form circular dimers. The clinical and laboratory findings support recent conclusions that Pearson syndrome is not confined to bone marrow and pancreas, as originally described, but is a multi-organ disorder associated with deletions in part of the mtDNA molecules. The tissue distribution and the relative proportions of the abnormal mtDNA molecules apparently determine the phenotype and clinical course.
authors.affiliation: Department of Paediatrics, University of Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: E
authors.initials: E
authors.lastname: Schoenle
authors.forename: P
authors.initials: P
authors.lastname: Tuchschmid
authors.forename: R
authors.initials: R
authors.lastname: Caduff
authors.forename: V
authors.initials: V
authors.lastname: Sabato
authors.forename: D
authors.initials: D
authors.lastname: DeMattia
authors.forename: R
authors.initials: R
authors.lastname: Gitzelmann
authors.forename: B
authors.initials: B
authors.lastname: Steinmann
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics; D000740:Anemia / Q000235:genetics; D001853:Bone Marrow / Q000002:abnormalities*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005198:Fanconi Syndrome / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis / Q000235:genetics; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D010182:Pancreatic Diseases / Q000235:genetics*; D000608:Renal Aminoacidurias / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D005319:Fetal Hemoglobin