Natural history of ROHHAD syndrome: development of severe insulin resistance and fatty liver disease over time

Abstract

Absract Background Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare syndrome with unknown etiology. Metabolic abnormalities are not known to be part of the syndrome. We present one of the oldest cases reported in the literature, who developed severe metabolic abnormalities and hepatic disease suggesting that these features may be part of the syndrome. Case presentation A 27-year-old woman, diagnosed with ROHHAD syndrome at age 15, who previously developed diabetes insipidus, growth hormone deficiency, hyperprolactinemia, and hypothyroidism in her first decade of life. This was followed by insulin resistance, NAFLD, liver fibrosis, and splenomegaly before age 14 years. Her regimen included a short course of growth hormone, and cyclic estrogen and progesterone. Her metabolic deterioration continued despite treatment with metformin. Interestingly, she had a favorable response to liraglutide therapy despite having a centrally mediated cause for her obesity. At age 26, a 1.6 cm lesion was found incidentally in her liver. Liver biopsy showed hepatocellular carcinoma which was successfully treated with radiofrequency ablation. Conclusion Metabolic abnormalities, Insulin resistance and fatty liver disease are potentially part of the ROHHAD syndrome that may develop over time. GLP1 agonists were reasonably effective to treat insulin resistance and hyperphagia. Patients with ROHHAD may benefit from close follow up in regards to liver disease. Electronic supplementary material The online version of this article (10.1186/s40842-019-0082-y) contains supplementary material, which is available to authorized users.

ROHHAD (Rapid-onset Obesity with Hypoventilation, Hypothalamic Dysfunction, Autonomic Dysregulation) Syndrome—What Every Pediatrician Should Know About the Etiopathogenesis, Diagnosis and Treatment: A Review

“…Insulin resistance, impaired glucose intolerance, diabetes mellitus, hypertriglyceridemia and progressive fatty liver disease were reported in several cases. 2 , 5 , 38 …”

“… Note: Data from these studies. 4 , 5 , 32 , 35 , 38 Abbreviations: EEG, electroencephalography; IGF-1, insulin-like growth factor 1; MIGB I 123 , metaiodobenzylguanidine iodine 123 ; MRI, magnetic resonance imaging. …”

“…Insulin resistance, diabetes mellitus, hypertriglyceridemia, progressive fatty liver disease, metabolic syndrome, bradycardia, cor pulmonale, right ventricular hypertrophy, pulmonary hypertension, heart failure and scoliosis have been described in patients with ROHHAD syndrome. 38,39,43,44 Mortality rate is high at 50-60%, due to hypoventilation, cardiopulmonary failure and cardiopulmonary arrest. 4,5,36…”

Rare Forms of Endocrine and Systemic Autoimmune Disorders

“…Genetic studies have failed in identifying reliable disease-associated variants, as well as alterations in epigenetic mechanisms affecting genes functionally linked to cellular and physiopathological processes altered in ROHHADNET (i.e., those involved in hypothalamic, autonomic, and neuroendocrine system development and function) (Jalal Eldin et al 2019;Giacomozzi et al 2019). Autoimmune predisposition precipitated by the exposure to environmental factors has been postulated, based on the presence of CSF oligoclonal bands; nonspecific signs of hypothalamic, pituitary stalk, and periaqueductal gray matter inflammation at MRI and autopsy; neural crest tumors (40% of the cases), known to trigger paraneoplastic syndrome; undetectable levels of hypocretin-1, considered to be secondary to an immune-mediated destruction of hypo-cretin neurons; association with other autoimmune disorders, like celiac disease; partial response to i.v.…”

ROHHAD Sendromlu Olgunun King’in Amaca Ulaşma Kuramına Dayalı Bakımının Planlanması

“…Genetik altyapısı kanıtlanamamakla birlikte, PHOX2B genindeki mutasyonun santral hipoventilasyona neden olduğu belirtilmektedir. Hastalıkla ilgili bilgiler çok azdır, bildirilen mortalite oranı ise %50-60'tan daha yüksektir (Jalal Eldin, 2019).…”