Anti-Hypothalamus and Anti-Pituitary Auto-antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis

Claudio Giacomozzi, Federica Guaraldi, Paola Cambiaso, Marcello Niceta, Elisabetta Verrillo, Marco Tartaglia, Renato Cutrera

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
JournalHormone Research in Paediatrics
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Cite this

Giacomozzi, Claudio ; Guaraldi, Federica ; Cambiaso, Paola ; Niceta, Marcello ; Verrillo, Elisabetta ; Tartaglia, Marco ; Cutrera, Renato. / Anti-Hypothalamus and Anti-Pituitary Auto-antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis. In: Hormone Research in Paediatrics. 2019.
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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.",
author = "Claudio Giacomozzi and Federica Guaraldi and Paola Cambiaso and Marcello Niceta and Elisabetta Verrillo and Marco Tartaglia and Renato Cutrera",
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Anti-Hypothalamus and Anti-Pituitary Auto-antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis. / Giacomozzi, Claudio; Guaraldi, Federica; Cambiaso, Paola; Niceta, Marcello; Verrillo, Elisabetta; Tartaglia, Marco; Cutrera, Renato.

In: Hormone Research in Paediatrics, 01.01.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Anti-Hypothalamus and Anti-Pituitary Auto-antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis

AU - Giacomozzi, Claudio

AU - Guaraldi, Federica

AU - Cambiaso, Paola

AU - Niceta, Marcello

AU - Verrillo, Elisabetta

AU - Tartaglia, Marco

AU - Cutrera, Renato

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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DO - 10.1159/000499163

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SN - 1663-2818

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