O'Connell Susan M, Johnson Stephanie R, Lewis Barry D, Staltari Louise, Peverall Joanne, Ly Trang, Martin Andrew C, Jones Timothy W, Price Glynis J, Murch Ashleigh, Choong Catherine S Y
Department of Endocrinology, Princess Margaret Hospital for Children, Perth, Western Australia, Australia. SusanMary.O'
J Pediatr Endocrinol Metab. 2011;24(7-8):555-9. doi: 10.1515/jpem.2011.230.
Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance presenting in infancy with renal salt wasting and failure to thrive. Here, we present the case of a 6-week-old baby girl who presented with mild hyponatraemia and dehydration with a background of severe failure to thrive. At presentation, urinary sodium was not measurably increased, but plasma aldosterone and renin were increased, and continued to rise during the subsequent week. Despite high calorie feeds the infant weight gain and hyponatraemia did not improve until salt supplements were commenced. Subsequently, the karyotype was reported as 46,XX,inv (4)(q31.2q35). A search of the OMIM database for related genes at or near the inversion breakpoints, showed that the mineralocorticoid receptor gene (NR3C2) at 4q31.23 was a likely candidate. Further FISH analysis showed findings consistent with disruption of the NR3C2 gene by the proximal breakpoint (4q31.23) of the inversion. There was no evidence of deletion or duplication at or near the breakpoint. This is the first report of a structural chromosome disruption of the NR3C2 gene giving rise to the classical clinical manifestations of pseudohypoaldosteronism type 1 in an infant.
I型假性醛固酮减少症（PHA1）是一种罕见的盐皮质激素抵抗形式，在婴儿期表现为肾性失盐和生长发育迟缓。在此，我们报告一例6周大女婴的病例，该患儿以严重生长发育迟缓为背景，出现轻度低钠血症和脱水。就诊时，尿钠未显著升高，但血浆醛固酮和肾素升高，并在随后一周持续上升。尽管给予高热量喂养，但在开始补充盐分之前，婴儿的体重增加和低钠血症并未改善。随后，核型报告为46,XX,inv(4)(q31.2q35)。在OMIM数据库中搜索倒位断点处或附近的相关基因，发现位于4q31.23的盐皮质激素受体基因（NR3C2）可能是候选基因。进一步的荧光原位杂交（FISH）分析显示，结果与倒位近端断点（4q31.23）破坏NR3C2基因一致。在断点处或附近没有缺失或重复的证据。这是首次报道NR3C2基因的结构性染色体破坏导致婴儿出现1型假性醛固酮减少症的典型临床表现。
