Tian Huining, Yan Zi, Lv You, Sun Lin, Gang Xiaokun, Wang Guixia
Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China.
Medicine (Baltimore). 2020 Oct 23;99(43):e22936. doi: 10.1097/MD.0000000000022936.
Kallmann syndrome (KS) is a rare inherited genetic disorder characterized by hypogonadotropic hypogonadism and hyposmia/anosmia. Early diagnosis is the key to timely treatment and improvement of prognosis in patients with KS. As the most common complication of KS, renal agenesis can provide clues to early diagnosis and treatment for KS. In this article, we report a case of KS with 8 rare urinary disorders for the first time.
A 19-year-old Chinese man presented with 8 rare urinary disorders and a history of bilateral cryptorchidism came to us for micropenis, hyposmia, and delayed puberty.
The patient presented with hyposmia, low levels of sex hormones and showed a weak response to the GnRH stimulation test leading to a diagnosis of KS. Two missense mutations were found in further whole-exome sequencing: 1) Kallmann syndrome 1 (KAL1) gene in exon11, c.1600G > A, p. Val534Ile; 2) Prokineticin receptor 2 (PROKR2) gene in exon 2, c.533G > A, p. Trp178Ser. which led to a diagnosis of KS.
The patient underwent replacement therapy of human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG). The patient had previously undergone six surgeries for cryptorchidism and urinary disorders.
The patient's puberty retardation was effectively alleviated. His serum testosterone (T) reached a normal level (8.280 nmol/mL). During the follow-up period, he presented with Tanner stage II pubic hair development.
In this article, we report 8 rare urinary disorders with missense mutations of KAL1 and PROKR2 in a case of KS. Among them, bilateral giant kidneys, urinary extravasation of right renal, bilateral megalo-ureters, left ureteral terminal obstruction, bilateral renal cyst and bladder emptying disorder are reported for the first time, which enrich the integrity of urinary disorder types and provide clues to genetic counseling in patients with KS.
卡尔曼综合征（KS）是一种罕见的遗传性疾病，其特征为低促性腺激素性性腺功能减退和嗅觉减退/嗅觉丧失。早期诊断是KS患者及时治疗并改善预后的关键。肾发育不全作为KS最常见的并发症，可为KS的早期诊断和治疗提供线索。在本文中，我们首次报道了一例伴有8种罕见泌尿系统疾病的KS病例。
一名19岁的中国男性因小阴茎、嗅觉减退和青春期延迟前来就诊，他患有8种罕见的泌尿系统疾病且有双侧隐睾病史。
患者表现为嗅觉减退、性激素水平低下，对促性腺激素释放激素（GnRH）刺激试验反应较弱，从而诊断为KS。在进一步的全外显子组测序中发现了两个错义突变：1）位于第11外显子的卡尔曼综合征1（KAL1）基因，c.1600G＞A，p.Val534Ile；2）位于第2外显子的促动力蛋白受体2（PROKR2）基因，c.533G＞A，p.Trp178Ser，这导致了KS的诊断。
患者接受了人绒毛膜促性腺激素（HCG）和人绝经期促性腺激素（HMG）替代治疗。该患者此前已因隐睾症和泌尿系统疾病接受了6次手术。
患者青春期发育迟缓得到有效缓解。他的血清睾酮（T）达到正常水平（8.280 nmol/mL）。在随访期间，他出现了坦纳Ⅱ期阴毛发育。
在本文中，我们报道了一例KS患者伴有KAL1和PROKR2错义突变的8种罕见泌尿系统疾病。其中，双侧巨大肾、右肾尿液外渗、双侧巨输尿管、左输尿管末端梗阻、双侧肾囊肿和膀胱排空障碍均为首次报道，丰富了泌尿系统疾病类型的完整性，并为KS患者的遗传咨询提供了线索。
