An autopsy case of an adult woman with Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHAD(NET)) syndrome developing nonalcoholic steatohepatitis and hepatocellular carcinoma: A case report.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC. METHODS: The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage. RESULTS: Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year. CONCLUSION: At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC.

3D fat-suppressed T1-weighted volume isotropic turbo spin-echo acquisition (VISTA) imaging for the evaluation of the ectopic posterior pituitary gland.

OBJECTIVE: We evaluated the usefulness of fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) imaging for the evaluation of the ectopic posterior pituitary gland (EPPG). MATERIALS AND METHODS: This retrospective study included 9 patients with EPPG due to causes other than tumor. All underwent sagittal two-dimensional (2D) T1W-, FS 3D T1W-VISTA- (VISTA), and 3D T2W-driven equilibrium radiofrequency reset pulse (DRIVE) imaging. Two radiologists independently reviewed the 2D T1W- and VISTA images for their image quality and for visualization of the EPPG and of pituitary stalk transection. DRIVE findings were used as the reference standard for pituitary stalk transection. Interobserver and intermodality agreements were evaluated with the kappa (κ) coefficient. The mean grade assigned to the 2D T1W- and the VISTA imaging technique for visualization of the EPPG was assessed by the Mann-Whitney U test. RESULTS: Interobserver agreement for visualization of the EPPG on 2D T1W- and VISTA images was excellent (κ = 0.82 and κ = 1.00, respectively). The mean grade for EPPG visualization was significantly higher for VISTA- than 2D T1W images (p = 0.0039). CONCLUSION: FS 3D T1W-VISTA imaging is useful for the evaluation of EPPG. Conventional MRI yields insufficient information for the evaluation of the ectopic posterior pituitary gland (EPPG). The visualization of the EPPG was significantly higher for fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) than 2D T1W images. FS 3D T1W-VISTA imaging is useful for the evaluation of the EPPG.

Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding.

Few data exists regarding the clinical impact of breastfeeding in infantile sitosterolaemic cases. We report four Japanese infantile cases of sitosterolaemia, an extremely rare inherited disease characterised by increased serum levels of plant sitosterol, presenting with severe hypercholesterolaemia and systemic xanthomas exacerbated by breastfeeding. In these four cases, genetic analyses were performed for low-density lipoprotein (LDL) receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor adaptor protein 1 and ATP-binding cassette (ABC) subfamily G member 5 and 8 (ABCG5 and ABCG8) genes. We assessed their clinical manifestations, including responsiveness to a variety of treatments, especially to weaning from breastfeeding and use of ezetimibe. Two pairs of mutations in the ABCG5 gene in each case, including two novel mutations (c.130C>T or p.Ser44Ala and c.1813_1817delCTTTT or p.Pro558GlufsX14) and two known mutations (c.1306G>A or p.Arg389His and c.1336C>T or p.Arg446X), were identified. Significant reductions in cholesterol levels were obtained by means of weaning from breastfeeding alone. Substantial reductions in sitosterol levels, without any apparent side effects, were observed with ezetimibe. In conclusion, we have identified infantile Japanese sitosterolaemic subjects with extreme hypercholesterolaemia exacerbated by breastfeeding. Their unique response to weaning from breastfeeding, as well as to use of ezetimibe, could provide insights into the metabolic basis of sterols in humans.