title: Biochemical abnormalities in Pearson syndrome.
abstract: Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, Utah; University of Milano, Milan, Italy.
authors.forename: Beatrice Letizia
authors.initials: BL
authors.lastname: Crippa
authors.forename: Eyby
authors.initials: E
authors.lastname: Leon
authors.forename: Amy
authors.initials: A
authors.lastname: Calhoun
authors.forename: Amy
authors.initials: A
authors.lastname: Lowichik
authors.forename: Marzia
authors.initials: M
authors.lastname: Pasquali
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000097:blood / Q000172:deficiency* / Q000652:urine; D000596:Amino Acids / Q000097:blood; D001706:Biopsy; D001774:Blood Chemical Analysis; D000080984:Congenital Bone Marrow Failure Syndromes; D005260:Female; D006801:Humans; D007223:Infant; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D028361:Mitochondrial Diseases / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D009135:Muscular Diseases / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
chemical_list: D000596:Amino Acids; D044942:Acyl-CoA Dehydrogenase, Long-Chain
keywords: Pearson syndrome; mitochondrial disease; organic aciduria; orotic acid; plasma amino acids; uridine