Background

Many central nervous system disorders result in hypothalamic-pituitary (HP) axis dysfunction. Alternating Hemiplegia of Childhood (AHC) is usually caused by mutations in the ATP1A3 subunit of the Na⁺/K⁺ ATPase, predominantly affecting GABAergic interneurons. GABAergic interneurons and the ATP1A3 subunit are both important for function of the hypothalamus. However, whether HP dysfunction occurs in AHC and, if so, how such dysfunction manifests remains to be investigated.

Methods

We conducted a retrospective review of a cohort of 50 consecutive AHC patients for occurrence of HP related manifestations and analyzed the findings of the 6 patients, from that cohort, with such manifestations.

Results

Six out of 50 AHC patients manifested HP dysfunction. Three of these patients were mutation positive and 3 were mutation negative. Of the 6 patients with HP dysfunction, 3 had central precocious puberty. A fourth had short stature due to growth hormone deficiency. Two other patients had recurrent episodes of fever of unknown origin (FUO) diagnosed, after workups, as being secondary to central fever. All patients were evaluated and co-managed by pediatric neurology and endocrinology or rheumatology.

Conclusion

AHC was associated with HP dysfunction in about 12% of patients. Awareness of such dysfunction is important for anticipatory guidance and management particularly in the case of FUO which often presents a diagnostic dilemma. Our findings are also consistent with current understandings of the underlying pathophysiology of AHC and of the HP axis.

中文翻译：

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儿童交替性偏瘫的下丘脑-垂体功能障碍

背景

许多中枢神经系统疾病会导致下丘脑-垂体（HP）轴功能障碍。儿童交替性偏瘫（AHC）通常是由Na ⁺ / K ⁺  ATPase的ATP1A3亚基突变引起的，主要影响GABA能中神经元。GABA能神经元和ATP1A3亚基对下丘脑的功能都很重要。但是，HP机能障碍是否在AHC中发生，如果发生，这种机能障碍如何表现尚待研究。

方法

我们对50例连续的AHC患者的HP相关表现​​进行了回顾性回顾，并分析了该队列中6例具有此类表现的患者的发现。

结果

50名AHC患者中有6名表现出HP功能障碍。这些患者中有3例为突变阳性，而3例为突变阴性。在6例HP功能障碍患者中，有3例为中枢性性早熟。四分之一由于生长激素缺乏而身材矮小。在检查后，另外两名患者被诊断出复发性发源性不明（FUO）发作为继发于中枢性发烧。所有患者均通过儿科神经内分泌科或风湿病科进行评估和共同管理。

结论

在大约12％的患者中，AHC与HP功能障碍有关。认识到这种功能障碍对于预期的指导和管理非常重要，尤其是对于经常表现出诊断难题的FUO。我们的发现也与当前对AHC和HP轴的潜在病理生理学的理解相一致。