This fascinating new case report from Jacobson et al. (10.1542/peds.2015-1080) takes a look at a case of rapid onset obesity. ROHHAD is an acronym for a syndrome usually presenting in the preschool years that stands for Rapid-onset Obesity, Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation. It is a progressive, potentially lethal condition.
ROHHAD’s etiology is still to be worked out, but it appears to be an immune mediated process resulting in an autoimmune encephalopathy. A subset of affected patients have a neural crest tumor that presumably precedes the onset of ROHHAD syndrome. In this subset, the syndrome may occur due to reactivity of the patient’s immune system to the presence of the neural crest tumor.
The model of opsoclonus /myoclonus in association with neuroblastoma, in which it is believed a tumor antigen triggers an immune response which then leads to not only a wanted immune attack on the tumor but also, (by way of molecular mimicry), an unwanted attack on the cerebellum, offers a plausible explanation for ROHHAD’s occurrence. In ROHHAD syndrome instead of the cerebellum being the target of the autoimmune attack, it is the hypothalamus.
The stem cell transplantation group at Johns Hopkins has developed a treatment protocol using high dose cyclophosphamide as a means of “resetting” the immune system and eliminating the aberrant clones of immunocytes involved in the autoimmune attack1. Jackson et al at The Kennedy-Kreiger Institute working with the Hopkins’s group have added objective data supporting the effectiveness of this treatment protocol.
Jackson not only documented a reduced appetite in association with decreasing BMI but also a reduction in the typical autistic-like behavior that ROHHAD patients develop with demonstrable improved neuropsychological performance. The improvement was sustained over the follow-up time of 15 months.
Where were the ROHHAD patients in years past? ROHHAD cannot possibly be a new disease if the conjectured mechanism is correct. I suspect the ROHHAD patients were out there hiding behind different names including hypothalamic injury from an undiagnosed infectious encephalitis or a Prader- Willi phenotype in an era before genetic confirmation was possible.
- Paz-Priel I, Cooke DW, Chen AR. Cyclophosphamide for Rapid-Onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Automatic Dysregulation Syndrome. J of Peds 2011;158:337-9