title: Childhood-onset autoimmune cytopenia as the presenting feature of biallelic ACP5 mutations.
abstract: Childhood-onset chronic and refractory cytopenias are rare and may be genetic in etiology. We report three pediatric cases of severe autoimmune thrombocytopenia or anemia associated with growth retardation and spastic diplegia with intracranial calcification. The identification of platyspondyly and metaphyseal lesions suggested a potential diagnosis of spondyloenchondrodysplasia (SPENCD), which was confirmed with the identification of biallelic ACP5 mutations. Two patients demonstrated elevated serum interferon alpha levels. Our report highlights ACP5-associated disease as a cause of childhood-onset autoimmune cytopenia, particularly combined with growth retardation and/or spasticity. Furthermore, a role for type I interferon in the pathogenesis of autoimmune cytopenias is supported.
authors.affiliation: Department of Pediatric Immunology, Hematology and Rheumatology, Hôpital Necker, APHP, Paris, France.
authors.forename: Anne-Sylvia
authors.initials: AS
authors.lastname: Sacri
authors.affiliation: Department of Pediatric Hematology Oncology, Clinique Universitaire Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Annelyse
authors.initials: A
authors.lastname: Bruwier
authors.affiliation: Department of Clinical Genetics, Hôpital Necker, APHP, Paris, France.|Institut IMAGINE, Paris, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Baujat
authors.affiliation: Department of Pediatric Radiology, Hôpital Necker, APHP, Paris.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Breton
authors.affiliation: Department of Pediatric Immunology, Hematology and Rheumatology, Hôpital Necker, APHP, Paris, France.|Institut IMAGINE, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.affiliation: Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.|Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Briggs
authors.affiliation: Department of Pediatric Immunology, Hematology and Rheumatology, Hôpital Necker, APHP, Paris, France.|Institut IMAGINE, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
mesh_terms: D017668:Age of Onset; D000483:Alleles; D001327:Autoimmune Diseases / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D000071681:Tartrate-Resistant Acid Phosphatase / Q000235:genetics*
chemical_list: C000605510:ACP5 protein, human; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: autoimmunity; cytopenia; interferon; spondyloenchondrodysplasia