Clinical Biochemistry, Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
University College London Hospitals NHS Foundation Trust, London, UK.
Pediatr Nephrol. 2017 Nov;32(11):2159-2163. doi: 10.1007/s00467-017-3741-1. Epub 2017 Jul 27.
A baby girl was born at 39 weeks gestation to consanguineous Asian parents. From day 1 of life she had severe hypoglycaemia with an inappropriately elevated insulin concentration consistent with congenital hyperinsulinism (CHI), confirmed by the finding of a homozygous mutation in ABCC8 (encoding the sulfonylurea receptor 1).
CASE DIAGNOSIS/TREATMENT: Urine organic acid analysis showed an incidentally elevated excretion of glycolate. Whilst this was unlikely to contribute to the hypoglycaemia, hyperglycolic aciduria is a known feature of primary hyperoxaluria type 1 (PH1); therefore oxalate was also measured in urine and found to be elevated. Sequence analysis of the genes involved in PH1 and also the two other known forms of primary hyperoxaluria revealed no pathological variants. PH1 was definitively excluded by enzyme activity analysis on a liver biopsy, which confirmed normal glyoxylate aminotransferase (AGT) activity and positive AGT immunoreactivity. Glycolate oxidase (GO) deficiency was considered, and thus gene sequencing of HAO1, which encodes GO, was performed. A homozygous change (c.493G>T p.(Gly165Cys)) was found in exon 3 of HAO1, predicted to be deleterious to protein function. Further analysis of the liver biopsy demonstrated absent GO enzyme activity, confirming GO deficiency in this case.
The results lead to the conclusion that this baby has two unrelated autosomal recessive conditions, CHI and GO deficiency, and also hyperoxaluria of unknown aetiology. Deficiency of GO is a very rare disorder with only two previously published cases. It is considered to be an essentially benign inborn error of metabolism. The present case is unique in that GO deficiency is associated with persistent hyperoxaluria.
一名女婴在妊娠 39 周时由近亲的亚裔父母出生。从出生第一天开始，她就出现严重低血糖，胰岛素浓度升高，与先天性高胰岛素血症（CHI）一致，这是由 ABCC8（编码磺酰脲受体 1）的纯合突变所证实的。
诊断/治疗：尿液有机酸分析显示，草酸盐的排泄量异常升高。虽然这不太可能导致低血糖，但高糖二酸尿症是 1 型原发性高草酸尿症（PH1）的已知特征；因此，尿液中也测量了草酸盐，发现其升高。PH1 相关基因以及另外两种已知的原发性高草酸尿症的序列分析未发现病理性变异。通过肝活检进行的 PH1 酶活性分析明确排除了 PH1，该分析证实了正常的乙醛酸氨基转移酶（AGT）活性和阳性 AGT 免疫反应性。考虑到草酸盐氧化酶（GO）缺乏症，因此对编码 GO 的 HAO1 基因进行了测序。在 HAO1 的外显子 3 中发现了一个纯合改变（c.493G>T p.（Gly165Cys）），预测对蛋白质功能具有有害性。对肝活检的进一步分析显示 GO 酶活性缺失，证实了这种情况下 GO 缺乏症的存在。
结果表明，这个婴儿同时患有两种无关的常染色体隐性疾病，即 CHI 和 GO 缺乏症，以及病因不明的高草酸尿症。GO 缺乏症是一种非常罕见的疾病，仅有两例先前发表的病例。它被认为是一种本质上良性的先天性代谢错误。本病例的独特之处在于 GO 缺乏症与持续性高草酸尿症有关。
