Department of Chemical Pathology, St Luke's Hospital, 801 Ostrum Street, Bethlehem, PA 18015, USA.
Ann Clin Biochem. 2010 May;47(Pt 3):279-81. doi: 10.1258/acb.2010.009250. Epub 2010 Apr 20.
There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.
人们对成人急性发作的先天性代谢缺陷认识不足，其中 X 连锁尿素循环缺陷精氨酰琥珀酸裂解酶（OTC）缺乏就是一个例子，已经发现许多相对轻微的突变。在男性半合子中，临床表现和发病年龄因突变而异。在女性杂合子中，临床表现取决于异常基因的表达程度。较轻的突变可能不会引起明显的临床症状，直到患者受到异常高的氮负荷时，才会出现严重的高氨血症，此时才会被识别。在急性发作期间，肝酶可能正常或仅轻度升高，偶尔伴有凝血功能障碍，但关键发现是高氨血症。具有这些较轻形式的男孩可能表现出异常行为，并被诊断为注意缺陷多动障碍。本案例说明了在非专科中心，OTC 缺乏症的迟发性表现如何难以与药物滥用、精神疾病或脑病区分开来。在出现不明原因的关键症状（特别是无腹泻的长时间呕吐和精神状态改变/幻觉）的成人中，如果不测量血氨，或者如果没有证据表明肝功能失代偿但发现血氨升高时，不能识别其重要性，可能会导致诊断延迟或漏诊。
