Alena Welters1, Ranna El-Khairi2, Antonia Dastamani2, Nadine Bachmann3, Carsten Bergmann3, Clare Gilbert2, Emma Clement4, Jane A Hurst4, Nada Quercia5,6, Jonathan D Wasserman7, Thomas Meissner1, Pratik Shah2,8, Sebastian Kummer1. 1. Department of General Paediatrics, Neonatology and Paediatric Cardiology, Medical Faculty, University Children's Hospital Düsseldorf, Düsseldorf, Germany. 2. Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. 3. Center for Human Genetics, Bioscientia, Ingelheim, Germany. 4. Department of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. 5. Department of Genetic Counselling, The Hospital for Sick Children, Toronto, Canada. 6. Department of Molecular Genetics, University of Toronto, Toronto, Canada. 7. Division of Endocrinology, The Hospital for Sick Children, Toronto, Canada. 8. Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health and Disease Section, UCL Great Ormond Street Institute of Child Health, London, UK.
Abstract
OBJECTIVE: Genetic aetiology remains unknown in up to 50% of patients with persistent hyperinsulinaemic hypoglycaemia (HH). Several syndromes are associated with HH. We report Rubinstein-Taybi syndrome (RSTS) as one of the possible causes of persistent HH. Early diagnosis and treatment of HH is crucial to prevent hypoglycaemic brain injury. DESIGN: Four RSTS patients with HH were retrospectively analysed. METHODS: Genetic investigations included next-generation sequencing-based gene panels and exome sequencing. Clinical characteristics, metabolic profile during hypoglycaemia and treatment were reviewed. RESULTS: Disease-related EP300 or CREBBP variants were found in all patients, no pathogenic variants were found in a panel of genes associated with non-syndromic HH. Two patients had classic manifestations of RSTS, three had choanal atresia or stenosis. Diagnosis of HH varied from 1 day to 18 months of age. One patient was unresponsive to treatment with diazoxide, octreotide and nifedipine, but responded to sirolimus. All required gastrostomy feeding. CONCLUSIONS: Given the rarity of RSTS (1:125 000) and HH (1:50 000), our observations indicate an association between these two conditions. We therefore recommend that clinicians should be vigilant in screening for HH in symptomatic infants with RSTS. In children with an apparent syndromic form of HH, RSTS should be considered in the differential diagnosis.
OBJECTIVE: Genetic aetiology remains unknown in up to 50% of patients with persistent hyperinsulinaemic hypoglycaemia (HH). Several syndromes are associated with HH. We report Rubinstein-Taybi syndrome (RSTS) as one of the possible causes of persistent HH. Early diagnosis and treatment of HH is crucial to prevent hypoglycaemic brain injury. DESIGN: Four RSTS patients with HH were retrospectively analysed. METHODS: Genetic investigations included next-generation sequencing-based gene panels and exome sequencing. Clinical characteristics, metabolic profile during hypoglycaemia and treatment were reviewed. RESULTS: Disease-related EP300 or CREBBP variants were found in all patients, no pathogenic variants were found in a panel of genes associated with non-syndromic HH. Two patients had classic manifestations of RSTS, three had choanal atresia or stenosis. Diagnosis of HH varied from 1 day to 18 months of age. One patient was unresponsive to treatment with diazoxide, octreotide and nifedipine, but responded to sirolimus. All required gastrostomy feeding. CONCLUSIONS: Given the rarity of RSTS (1:125 000) and HH (1:50 000), our observations indicate an association between these two conditions. We therefore recommend that clinicians should be vigilant in screening for HH in symptomatic infants with RSTS. In children with an apparent syndromic form of HH, RSTS should be considered in the differential diagnosis.
Authors: Kara E Boodhansingh; Zhongying Yang; Changhong Li; Pan Chen; Katherine Lord; Susan A Becker; Lisa J States; N Scott Adzick; Tricia Bhatti; Show-Ling Shyng; Arupa Ganguly; Charles A Stanley; Diva D De Leon Journal: Eur J Endocrinol Date: 2022-06-27 Impact factor: 6.558
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