title: Systemic hyalinosis: a distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2).
abstract: OBJECTIVE
  We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.
  
  
  METHODS
  We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis.
  
  
  RESULTS
  We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease.
  
  
  CONCLUSIONS
  Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA.
authors.forename: Joseph T C
authors.initials: JT
authors.lastname: Shieh
authors.forename: Petra
authors.initials: P
authors.lastname: Swidler
authors.forename: John A
authors.initials: JA
authors.lastname: Martignetti
authors.forename: Maria Celeste M
authors.initials: MC
authors.lastname: Ramirez
authors.forename: Imelda
authors.initials: I
authors.lastname: Balboni
authors.forename: Julie
authors.initials: J
authors.lastname: Kaplan
authors.forename: Jeanette
authors.initials: J
authors.lastname: Kennedy
authors.forename: Omar
authors.initials: O
authors.lastname: Abdul-Rahman
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Enns
authors.forename: Christy
authors.initials: C
authors.lastname: Sandborg
authors.forename: Anne
authors.initials: A
authors.lastname: Slavotinek
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Hoyme
mesh_terms: D017668:Age of Onset; D005260:Female; D006801:Humans; D006818:Hyalin; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D018000:Receptors, Peptide
chemical_list: C447150:ANTXR2 protein, human; D008565:Membrane Proteins; D018000:Receptors, Peptide