Hague Jennifer, Casey Ruth, Bruty Jonathan, Legerton Tom, Abbs Stephen, Oddy Susan, Powlson Andrew S, Majeed Mohamed, Gurnell Mark, Park Soo-Mi, Simpson Helen
Departments of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Departments of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Endocrinol Diabetes Metab Case Rep. 2018 Feb 9;2018. doi: 10.1530/EDM-17-0139. eCollection 2018.
Activating mutations in are associated with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). NSIAD causes hyponatremia, decreased serum osmolality and clinical symptoms, which may present from birth or in infancy and include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life are often less specific and include malaise, dizziness, confusion, tiredness and headache. NSIAD is a rare X-linked condition, which is associated with a variable phenotype in males, of whom some present in infancy but others do not become symptomatic until adulthood, or occasionally, never. Female carriers may present with episodes of hyponatremia, usually found incidentally. Literature in this field is limited; namely, two clinical reports describing a female proband, both diagnosed in infancy. We describe, for the first time, the case of an adult female proband with NSIAD, who had longstanding associated symptoms of tiredness, headache, temporary memory loss and mood changes as well as hyponatremia and decreased serum osmolality. A water load test demonstrated an inability to dilute urine and gene sequencing confirmed a recurrent activating mutation in . The variant was inherited from the proband's mother who had had longstanding episodes of transient asymptomatic hyponatremia. This is the third report of a female proband with NSIAD and is the first female reported who sought medical treatment for chronic symptoms from adulthood. This case acts as a reminder of the importance of considering NSIAD as a diagnosis in females of all ages with unexplained hyponatremia.
Activating mutations in the gene are associated with the rare X-linked condition nephrogenic syndrome of inappropriate antidiuresis.NSIAD is associated with hyponatremia, decreased serum osmolality and inappropriately increased urinary osmolality. Early clinical symptoms in infancy include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life include malaise, dizziness, confusion, tiredness and headache.NSIAD should be considered in female, as well as male, patients who present with unexplained hyponatremia and decreased serum osmolality. Family history may reveal relevant symptoms or biochemical features in other family members. However, family history may not always be informative due to the variable nature of the condition or if the proband has a pathogenic variant.A water load test with measurement of AVP may be informative in distinguishing NSIAD from SIADH. Measurement of co-peptin levels may be considered, in substitution for direct measurement of AVP.Patients with NSIAD should be counseled about appropriate daily fluid volume intake. Potential episodes of fluid overload should be avoided.
[基因名称]中的激活突变与抗利尿激素分泌失调综合征（NSIAD）相关。NSIAD可导致低钠血症、血清渗透压降低及临床症状，这些症状可在出生时或婴儿期出现，包括肌张力减退、易激惹、呕吐和/或惊厥。成年后的症状通常不那么特异，包括不适、头晕、意识模糊、疲倦和头痛。NSIAD是一种罕见的X连锁疾病，男性患者的表型各异，有些在婴儿期发病，而另一些直到成年才出现症状，或偶尔从不出现症状。女性携带者可能会出现低钠血症发作，通常是偶然发现。该领域的文献有限；具体而言，有两份临床报告描述了一名女性先证者，均在婴儿期被诊断。我们首次描述了一名成年女性NSIAD先证者的病例，她长期存在疲倦、头痛、短暂性记忆丧失和情绪变化等相关症状，同时伴有低钠血症和血清渗透压降低。水负荷试验显示其无法稀释尿液，基因测序证实[基因名称]中存在复发性激活突变。该变异来自先证者的母亲，她曾长期出现短暂无症状性低钠血症发作。这是第三例女性NSIAD先证者的报告，也是首例因成年期慢性症状寻求治疗的女性报告。该病例提醒人们，对于所有年龄段不明原因低钠血症的女性，考虑NSIAD作为诊断的重要性。
[基因名称]中的激活突变与罕见的X连锁疾病抗利尿激素分泌失调综合征相关。NSIAD与低钠血症、血清渗透压降低和尿渗透压不适当升高有关。婴儿期的早期临床症状包括肌张力减退、易激惹、呕吐和/或惊厥。成年后的症状包括不适、头晕、意识模糊、疲倦和头痛。对于出现不明原因低钠血症和血清渗透压降低的女性及男性患者，均应考虑NSIAD。家族史可能揭示其他家庭成员的相关症状或生化特征。然而，由于该疾病的多变性或先证者具有[基因名称]致病变异，家族史可能并不总是提供有用信息。测量抗利尿激素（AVP）的水负荷试验可能有助于区分NSIAD和抗利尿激素分泌异常综合征（SIADH）。可考虑测量 copeptin 水平以替代直接测量 AVP。应建议NSIAD患者适当控制每日液体摄入量。应避免潜在的液体过载发作。
