#1778 A rare case of Kallmann syndrome combined with primary membranous nephropathy

Le résumé fourni par la source

Abstract Background and Aims Kallmann Syndrome (KS) is a rare genetic disorder characterized by hypogonadotropic hypogonadism and anosmia, resulting from defective migration of GnRH neurons and olfactory bulb development. Primary Membranous Nephropathy (PMN) is a common cause of nephrotic syndrome, characterized by thickening of the glomerular basement membrane and proteinuria. The co-occurrence of these two conditions has not been previously reported in the literature. This case report presents a rare instance of KS combined with PMN, and their potential pathophysiological relationship remains unclear, the AMER1 gene mutation may be a mutation point related to KS. Method A 37-year-old male presented with bilateral lower extremity edema for 1 year, which aggravated in the past 1 week. He was diagnosed with KS in our hospital 5 years ago and without any treatment currently. Comprehensive evaluations were performed, including: Clinical assessment: Detailed history, physical examination, and evaluation of KS-related features (anosmia, hypogonadism). Laboratory tests: Urinalysis, 24-hour urine protein quantification, blood routine, liver function, blood lipid, serum albumin, and sex hormone levels, and Anti-phospholipase A2 receptor (PLA2R) antibody assay. Imaging studies: Electrocardiogram, renal and cardiac ultrasound, chest CT, and brain MRI; Renal biopsy: Histopathological, immunofluorescence and electric mirror examination. Others: Genetic testing. Results The patient exhibited symptoms of nephrotic syndrome, including edema of both lower limbs, proteinuria (19 g/24 h), hypoalbuminemia (27.8 g/L), and hyperlipidemia; The renal biopsy pathological results (Fig. 1) and increased PLA2R (Table 1) clearly indicated that the patient was diagnosed with primary membranous nephropathy. After hormone and tacrolimus treatment, the patient achieved partial remission of nephrotic syndrome (Table 1). The patient had concurrent symptoms of KS. He had lost his sense of smell since childhood and had slower development than his peers with no development of secondary sexual characteristics at the age of 14. Small penis and testicles were investigated in our patient. Relevant hormone tests showed significantly reduced testosterone (0.32 ng/ml) and luteinizing hormone (0.29 mIU/ml), while the levels of other hormones such as estrogen, growth hormone were normal. And abdominal ultrasound indicated the absence of the left kidney, and the Cardiac ultrasound showed dextrocardia (Fig. 2). The diagnosis of KS in this patient is clear. To further investigate the cause of the patient's KS and whether there is an association between KS and PMN, we performed whole-exon sequencing on the patient and his parents. The patient did not see any of mutations in KS reported so far,but the patient was found to have a missense variant mutation in the AMER1 gene with 100% mutation abundance in whole-exon sequencing (Table 2). AMER1 is located on the X chromosome and it plays an important role in the middle stage of embryonic development. There is no reported indication that the AMER1 gene is related to KS, but the gene is specifically expressed in the nervous system and nasal epithelium, and is also widely expressed in the gonads and kidneys, which are highly overlapping with the target organs of KS, and the association with KS needs to be further investigated. Unfortunately, no similar mutations were found in his parents. Whether this patient is the precursor of KS caused by AMER1 gene mutation and the mechanism of its occurrence cannot be clarified at present, and it needs to be verified by the offspring or other cases or animal experiments. Conclusion In conclusion, this case is the first reported case of KS combined with primary membranous nephropathy, and the missense base mutation of AMER1 is expected to be a novel mutation site in KS patients, which needs to be verified in subsequent cases.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.