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Precision treatment of Singleton Merten syndrome with ruxolitinib: a case report.
Broser, Philip; von Mengershausen, Ursula; Heldt, Katrin; Bartholdi, Deborah; Braun, Dominique; Wolf, Christine; Lee-Kirsch, Min Ae.
Afiliação
  • Broser P; Department of Pediatric Neurology, Children's Hospital of Eastern Switzerland, Sankt Gallen, Switzerland. philip.broser@me.com.
  • von Mengershausen U; Department of Pediatric Neurology, Children's Hospital of Eastern Switzerland, Sankt Gallen, Switzerland.
  • Heldt K; Department of Pediatric Endocrinology, Children's Hospital of Eastern Switzerland, Sankt Gallen, Switzerland.
  • Bartholdi D; Department of Human Genetics, University Hospital Bern, Bern, Switzerland.
  • Braun D; Department of Human Genetics, University Hospital Bern, Bern, Switzerland.
  • Wolf C; Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
  • Lee-Kirsch MA; Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Pediatr Rheumatol Online J ; 20(1): 24, 2022 Apr 11.
Article em En | MEDLINE | ID: mdl-35410415
BACKGROUND: Singleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation. CASE PRESENTATION: We report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/ß receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved. CONCLUSIONS: JAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoporose / Interferon Tipo I Limite: Child / Child, preschool / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoporose / Interferon Tipo I Limite: Child / Child, preschool / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article