HSD17B4基因突变致D-双功能蛋白缺乏症

杨树梅; 曹传顶; 丁颖; 王铭杰; 岳少杰

doi:10.7499/j.issn.1008-8830.2107158

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中国当代儿科杂志 ›› 2021, Vol. 23 ›› Issue (10) : 1058-1063. DOI: 10.7499/j.issn.1008-8830.2107158

论著·疑难病研究

HSD17B4基因突变致D-双功能蛋白缺乏症

杨树梅, 曹传顶, 丁颖, 王铭杰, 岳少杰

作者信息 +

D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate

YANG Shu-Mei, CAO Chuan-Ding, DING Ying, WANG Ming-Jie, YUE Shao-Jie

Author information +

文章历史 +

摘要

15 d男性患儿，因反复抽搐14 d入院。主要临床表现为难治性癫痫发作、反应差、喂养困难、四肢肌张力低、双侧听力受损，神经电生理表现为双侧脑干听觉诱发电位减弱及脑电图爆发-抑制图形，血清极长链脂肪酸提示二十六烷酸显著增高，基因检测提示HSD17B4基因c.101C>T(p.Ala34Val)，c.1448_1460del(p.Ala483Aspfs*37)复合杂合突变。该文报道1例HSD17B4基因突变所致D-双功能蛋白缺乏症，对该病流行病学、临床特征及诊疗进行归纳总结，重点关注与大田原综合征的鉴别，为该病早期诊断提供了参考依据。

Abstract

A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the HSD17B4 gene. This article reports a case of D-bifunctional protein deficiency caused by HSD17B4 gene mutation and summarizes the epidemiological and clinical features, diagnosis, and treatment of this disease, with a focus on the differential diagnosis of this disease from Ohtahara syndrome.

导出引用

杨树梅, 曹传顶, 丁颖, 王铭杰, 岳少杰. HSD17B4基因突变致D-双功能蛋白缺乏症[J]. 中国当代儿科杂志. 2021, 23(10): 1058-1063 https://doi.org/10.7499/j.issn.1008-8830.2107158

YANG Shu-Mei, CAO Chuan-Ding, DING Ying, WANG Ming-Jie, YUE Shao-Jie. D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate[J]. Chinese Journal of Contemporary Pediatrics. 2021, 23(10): 1058-1063 https://doi.org/10.7499/j.issn.1008-8830.2107158

参考文献

1 Ferdinandusse S, Denis S, Mooyer PAW, et al. Clinical and biochemical spectrum of D-bifunctional protein deficiency[J]. Ann Neurol, 2006, 59(1): 92-104. PMID: 16278854. DOI: 10.1002/ana.20702.
2 Watkins PA, Chen WW, Harris CJ, et al. Peroxisomal bifunctional enzyme deficiency[J]. J Clin Invest, 1989, 83(3): 771-777. PMID: 2921319. PMCID: PMC303746. DOI: 10.1172/JCI113956.
3 Chen S, Du LR, Lei YH, et al. Two novel HSD17B4 heterozygous mutations in association with D-Bifunctional protein deficiency: a case report and literature review[J]. Front Pediatr, 2021, 9: 679597. PMID: 34368026. PMCID: PMC8342883. DOI: 10.3389/fped.2021.679597.
4 向秋莲, 郭虎, 高修成, 等. HSD17B4新突变致过氧化物酶体D-双功能蛋白缺乏症一家系并文献复习[J]. 中华实用儿科临床杂志, 2021, 36(10): 772-775. DOI: 10.3760/cma.j.cn101070-20200914-01511.
5 Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30.
6 van Karnebeek CDM, Tiebout SA, Niermeijer J, et al. Pyridoxine-dependent epilepsy: an expanding clinical spectrum[J]. Pediatr Neurol, 2016, 59: 6-12. PMID: 26995068. DOI: 10.1016/j.pediatrneurol.2015.12.013.
7 Lee RR, Raymond GV. Child neurology: Zellweger syndrome[J]. Neurology, 2013, 80(20): e207-e210. PMID: 23671347. PMCID: PMC3908348. DOI: 10.1212/WNL.0b013e3182929f8e.
8 Turk BR, Theda C, Fatemi A, et al. X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies[J]. Int J Dev Neurosci, 2020, 80(1): 52-72. PMID: 31909500. PMCID: PMC7041623. DOI: 10.1002/jdn.10003.
9 Motley AM, Tabak HF, Smeitink JA, et al. Non-rhizomelic and rhizomelic chondrodysplasia punctata within a single complementation group[J]. Biochim Biophys Acta, 1996, 1315(3): 153-158. PMID: 8611652. DOI: 10.1016/0925-4439(95)00114-x.
10 M?ller G, van Grunsven EG, Wanders RJ, et al. Molecular basis of D-bifunctional protein deficiency[J]. Mol Cell Endocrinol, 2001, 171(1/2): 61-70. PMID: 11165012. DOI: 10.1016/s0303-7207(00)00388-9.
11 Klouwer FCC, Huffnagel IC, Ferdinandusse S, et al. Clinical and biochemical pitfalls in the diagnosis of peroxisomal disorders[J]. Neuropediatrics, 2016, 47(4): 205-220. PMID: 27089543. DOI: 10.1055/s-0036-1582140.
12 冉颜, 吕远, 白华, 等. 一例早发癫痫性脑病42型患儿的临床表型及基因变异分析[J]. 中华医学遗传学杂志, 2021, 38(2): 127-130. PMID: 33565063. DOI: 10.3760/cma.j.cn511374-20201022-00743.
13 Olson HE, Kelly M, LaCoursiere CM, et al. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression[J]. Ann Neurol, 2017, 81(3): 419-429. PMID: 28133863. PMCID: PMC5366084. DOI: 10.1002/ana.24883.
14 Kim HJ, Yang D, Kim SH, et al. Clinical characteristics of KCNQ2 encephalopathy[J]. Brain Dev, 2021, 43(2): 244-250. PMID: 32917465. DOI: 10.1016/j.braindev.2020.08.015.
15 Nascimento J, Mota C, Lacerda L, et al. D-bifunctional protein deficiency: a cause of neonatal onset seizures and hypotonia[J]. Pediatr Neurol, 2015, 52(5): 539-543. PMID: 25882080. DOI: 10.1016/j.pediatrneurol.2015.01.007.
16 Steinberg S, Jones R, Tiffany C, et al. Investigational methods for peroxisomal disorders[J]. Curr Protoc Hum Genet, 2008, Chapter 17: Unit 17.6. PMID: 18633975. DOI: 10.1002/0471142905.hg1706s58.
17 Cornet MC, Cilio MR. Genetics of neonatal-onset epilepsies[J]. Handb Clin Neurol, 2019, 162: 415-433. PMID: 31324323. DOI: 10.1016/B978-0-444-64029-1.00020-5.