A Rare Case of Paraganglioma Syndrome Associated With Polycythemia and Blindness.

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. They can be diagnosed independently or as part of a syndrome, especially with germline mutations. Rarely, a somatic mutation can present as part of a syndrome associated with recurrent PPGL, congenital polycythemia, and vascular malformation. We report a case of a 44-year-old man with a history of congenital blindness, stroke in utero, cerebral ataxia, and polycythemia since age 12, treated with phlebotomies who presented with back pain and hypertension. Abdominal computer tomography with IV contrast showed a right adrenal enhancing lesion measuring 1.4 x 1.2 cm and a conglomerate of heterogeneously enhancing periaortic lesions measuring up to 5 cm in the mid-abdomen. Biochemical workup revealed plasma free normetanephrine 27.5 nmol/L (0.00-0.89) and plasma free metanephrine 0.49 nmol/L (0.00-0.49). Histopathology confirmed synchronous pheochromocytoma and paraganglioma. This case illustrates the importance of taking a detailed past medical history and the relevance of polycythemia in the paraganglioma workup.

Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis.

Kelch-like 10 (KLHL10) is a member of the BTB (Bric-a-brac, Tramtrack, and Broad-Complex)-kelch protein superfamily essential for spermiogenesis and male fertility. In a search for KLHL10-interacting proteins using a yeast two-hybrid assay, we identified Cullin3 (CUL3) as one of multiple KLHL10-interacting partners. Yeast cotransformation assays revealed that CUL3 bound the BTB/POZ domain of KLHL10. Northern blot and quantitative RT-PCR analyses demonstrated that Cul3 mRNA was preferentially expressed in the testis. In situ hybridization analysis localized Cul3 mRNA to spermatids in the adult testis. CUL3 protein was detected in elongating and elongated spermatids (steps 10-16) by immunofluorescent microscopy. The expression pattern of CUL3 resembles KLHL10. CUL3 was coimmunoprecipated with KLHL10, and KLHL10 was also detected in the CUL3 immunoprecipitants using testis lysates. These findings suggest that KLHL10, like other BTB/kelch proteins, interacts with CUL3 to form a CUL3-based ubiquitin E3 ligase that functions specifically in the testis to mediate protein ubiquitination during spermiogenesis.