Chan Melanie M Y, Barnicoat Angela, Mumtaz Faiz, Aitchison Michael, Side Lucy, Brittain Helen, Bates Alan W H, Gale Daniel P
Centre for Nephrology, University College London, Royal Free Hospital, London, UK.
Northeast Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.
BMC Med Genet. 2017 Jul 26;18(1):79. doi: 10.1186/s12881-017-0436-1.
Fumarate hydratase (FH) deficiency is a rare autosomal recessive disorder which results in a major defect in cellular metabolism. It presents in infancy with progressive encephalopathy, hypotonia, seizures and failure to thrive and is often fatal in childhood. It is caused by mutations in the FH gene (1q42.1) that result in deficiency of the citric acid cycle enzyme fumarate hydratase, resulting in accumulation of fumaric acid. Heterozygous germline mutations in the FH gene predispose to an aggressive autosomal dominant inherited early-onset kidney cancer syndrome: hereditary leiomyomatosis and renal cell cancer (HLRCC).
Cascade FH mutation screening enabled the early diagnosis of a renal tumour in an asymptomatic parent of a child with fumarate hydratase deficiency, resulting in timely and possibly life-saving treatment.
While the theoretical risk of kidney cancer in parents of children with recessive fumarate hydratase deficiency is well recognized, to our knowledge this is the first report of a kidney tumour being detected in a parent by screening performed for this indication. This underscores the importance of offering lifelong kidney surveillance to such parents and other heterozygous relatives of children born with fumarate hydratase deficiency.
延胡索酸水合酶（FH）缺乏症是一种罕见的常染色体隐性疾病，会导致细胞代谢出现重大缺陷。其在婴儿期表现为进行性脑病、肌张力减退、癫痫发作和生长发育迟缓，常在儿童期致命。它由FH基因（1q42.1）突变引起，导致柠檬酸循环酶延胡索酸水合酶缺乏，从而致使富马酸积累。FH基因的杂合种系突变易引发侵袭性常染色体显性遗传的早发性肾癌综合征：遗传性平滑肌瘤病和肾细胞癌（HLRCC）。
通过级联FH突变筛查，在一名患有延胡索酸水合酶缺乏症儿童的无症状父母中早期诊断出肾肿瘤，从而实现了及时且可能挽救生命的治疗。
虽然隐性延胡索酸水合酶缺乏症患儿父母患肾癌的理论风险已得到充分认识，但据我们所知，这是首次通过针对该指征进行的筛查在父母中检测到肾肿瘤的报告。这凸显了为这些父母以及出生时患有延胡索酸水合酶缺乏症儿童的其他杂合亲属提供终身肾脏监测的重要性。
