Hormone Research in Paediatrics
Novel Insights from Clinical Practice / Case Report
Anti-Hypothalamus and Anti-Pituitary Autoantibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune EtiopathogenesisGiacomozzi C.a · Guaraldi F.b · Cambiaso P.c · Niceta M.d · Verrillo E.d,e · Tartaglia M.d · Cutrera R.d,eaUnit of Pediatrics, ASST-Mantova Carlo Poma Hospital, Mantova, Italy
bPituitary Unit, IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy cUnit of Endocrinology and Diabetes, Bambino Gesù Children’s Hospital, Rome, Italy dGenetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, Rome, Italy eRespiratory Unit, Pediatric Academic Department, Bambino Gesù Children’s Hospital, Rome, Italy |
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Article / Publication Details
Received: April 25, 2018
Accepted: February 27, 2019
Published online: April 30, 2019
Issue release date: January 2020
Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 3
ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)
For additional information: https://www.karger.com/HRP
Abstract
Background: Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a very rare and complex pediatric syndrome characterized by altered hypothalamic thermal regulation, pain threshold, and respiratory control, hyperphagia with rapid weight gain and, often, hypothalamic-pituitary dysfunction. Its etiopathogenesis remains undetermined. We investigated the presence of alterations to target genes and hypothalamic-pituitary autoimmunity in a patient with ROHHAD syndrome. Methods: A 3-year-old girl presenting with obesity after rapid weight gain was diagnosed with ROHHAD syndrome based on clinical features and abnormal biochemical and functional testing results. Because of worsening of rapid symptoms and demonstration of oligoclonal bands on cerebrospinal fluid (CSF) analysis, she was treated with plasmapheresis, methylprednisolone, anti-CD20 monoclonal antibodies, and azathioprine. Despite initial partial clinical improvement, the patient soon died of cardiorespiratory arrest. Post-mortem, whole exome sequencing, high-resolution comparative genomic hybridization array, and optimized indirect immunofluorescence (IIF) analysis were performed on blood and CSF. Results: No putative causative genomic variants compatible with dominant or recessive inheritance nor clinically significant structural rearrangement were detected. IIF on serum and CSF demonstrated the presence of anti-pituitary and anti-hypothalamus autoantibodies. Conclusions: These findings support the involvement of autoimmunity in ROHHAD syndrome. However, response to immunosuppressive treatment was only transient and the patient died. Further cases are required to define the complex disease pathogenesis.
© 2019 S. Karger AG, Basel
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Article / Publication Details
Received: April 25, 2018
Accepted: February 27, 2019
Published online: April 30, 2019
Issue release date: January 2020
Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 3
ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)
For additional information: https://www.karger.com/HRP
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