Yonatan Yeshayahu1, Roy Asaf2, Gal Dubnov-Raz2, Ginette Schiby3, Amos J Simon4, Atar Lev4, Raz Somech4. 1. 1] Pediatric Department, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel [2] Pediatric Endocrinology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 2. Pediatric Department, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. 1] Pediatric Department, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel [2] Cancer Research Center, Pediatric Immunology Service, Jeffrey Modell Foundation (JMF) Center, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
BACKGROUND: Glucose-6-phosphatase-β (G6PC3) deficiency is characterized by congenital neutropenia and variable developmental disorders, including those of the cardiovascular system and the urogenital system (e.g., cryptorchidism) and a peculiar visibility of subcutaneous veins. METHODS: A patient with clinical findings suggestive of G6PC3 deficiency was investigated. Genetic, hematopathologic, immunologic, and endocrine work-up were performed. RESULTS: The reported patient had binucleotide deletion mutation in G6PC3 and displayed the full spectrum of clinical manifestations associated with G6PC3 deficiency including neutropenia. The reported patient had normal bone marrow cellularity without increased apoptosis, and his neutrophils displayed normal respiratory burst activity. Endocrine work-up revealed low testosterone levels, which did not respond to human chorionic gonadotropin stimulation, extremely elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and undetectable anti-Müllerian hormone, all of which are suggestive of testicular failure or anorchia. CONCLUSION: Our report extends the knowledge about this syndrome and suggests a role for G6PC3 in testicular differentiation and formation. Urogenital dysmorphism could indeed be unrelated to G6PC3 and secondary to consanguinity. However, given the similar description of urogenital anomalies in previous reports of this syndrome, the dysmorphism in our patient is likely related.
BACKGROUND: Glucose-6-phosphatase-β (G6PC3) deficiency is characterized by congenital neutropenia and variable developmental disorders, including those of the cardiovascular system and the urogenital system (e.g., cryptorchidism) and a peculiar visibility of subcutaneous veins. METHODS: A patient with clinical findings suggestive of G6PC3 deficiency was investigated. Genetic, hematopathologic, immunologic, and endocrine work-up were performed. RESULTS: The reported patient had binucleotide deletion mutation in G6PC3 and displayed the full spectrum of clinical manifestations associated with G6PC3 deficiency including neutropenia. The reported patient had normal bone marrow cellularity without increased apoptosis, and his neutrophils displayed normal respiratory burst activity. Endocrine work-up revealed low testosterone levels, which did not respond to human chorionic gonadotropin stimulation, extremely elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and undetectable anti-Müllerian hormone, all of which are suggestive of testicular failure or anorchia. CONCLUSION: Our report extends the knowledge about this syndrome and suggests a role for G6PC3 in testicular differentiation and formation. Urogenital dysmorphism could indeed be unrelated to G6PC3 and secondary to consanguinity. However, given the similar description of urogenital anomalies in previous reports of this syndrome, the dysmorphism in our patient is likely related.