Novel variants in aromatic L-amino acid decarboxylase deficiency: Case report of sisters with mild phenotype

BackgroundAromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other hand, patients with a mild phenotype with AADC deficiency have been reported, but they number only a few cases. Therefore, the variation of phenotypes of the disease appears to be broad, and it may be challenging to diagnose an atypical phenotype as AADC deficiency.Case reportWe report novel compound heterozygous variants in DDC (c.202G > A and c.254C > T) in two sisters, whose main complaint was mild developmental delay, by whole-exome sequencing (WES). Additionally, we describe their clinical features and provide an image that shows the variants located at different sites responsible for the catalysis of AADC in a three-dimensional structure. The patients were prescribed a Monoamine oxidase (MAO) inhibitor after diagnosis.InterpretationOur cases indicate that a comprehensive genomic approach helps to diagnose AADC deficiency with atypical features, and underscore the significance of understanding the variations of this disorder for diagnosis and appropriate treatment.     

基于TCA循环关键酶测定研究督灸治疗早期强直性脊柱炎患者关节活动度的疗效及机制＊

目的 基于TCA循环（三羧酸循环，tricarboxylic acid cycle）关键酶测定研究督灸治疗早期强直性脊柱炎（AS）肾虚督寒证患者关节活动度的疗效及生物学机制。方法 110例早期AS肾虚督寒证患者随机分为观察组和对照组，各55例。对照组口服甲氨蝶呤+洛索洛芬钠，观察组在对照组治疗基础上给予督灸，疗程均为12周。观察治疗前后患者的病情活动指数（bath ankylosing spondylitis disease activity index，BASDAI）、功能指数（bath ankylosing spondylitis fundation index，BASFI）、活动度衡量指数（bath ankylosing measure index activity index，BASMI）、总和指数（bath ankylosing spondylitis patient slobal，BAS-G）、指-地距、枕-墙距、胸廓活动度、Schober试验水平和早期AS肾虚督寒证中医辨证（肾虚督寒证）评分；检测血清炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-18（IL-18）、血沉（ESR）和C-反应蛋白（CRP）含量；检测TCA循环关键酶柠檬酸合成酶（citrate synthase，CS）、异柠檬酸脱氢酶（isocitrate dehydrogenase，IDH）及α-酮戊二酸脱氢酶（α-ketoglutarate dehydrogenase，α-KGDHC）的水平；比较治疗12周患者的临床疗效及随访6个月复发率。结果 临床研究过程脱落6例。观察组总有效率96.2%，明显高于观察组的82.4%（P<0.05）；观察组随访6个月复发率5.7%，明显低于对照组的21.6%（P<0.05）。治疗12周后，观察组患者BASDAI、BASFI、BASMI、BAS-G、指-地距、枕-墙距和肾虚督寒证评分较对照组明显下降（P<0.05），胸廓活动度和Schober试验较对照组明显升高（P<0.05）；观察组患者TNF-α、IL-18、ESR、CRP、CS和IDH水平较对照组明显下降（P<0.05），α-KGDHC水平较对照组明显升高（P<0.05）。结论 督灸可以有效改善早期AS肾虚督寒证患者的临床症状，复发率低，值得临床推广应用。     

European Reference Network for Rare Vascular Diseases (VASCERN): When and how to use intravenous bevacizumab in Hereditary Haemorrhagic Telangiectasia (HHT)?

Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular multisystemic disease that leads to epistaxis, anaemia due to blood loss, and arteriovenous malformations (AVMs) in organs such as the lungs, liver and brain. HHT prevalence is estimated at 1/6000, i.e. around 85,000 European citizens, and is served by the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN). HHT treatments depend on clinical manifestations, and span multiple different medical, surgical and interventional disciplines. Separate to local treatments in the nose, in severe settings, intravenous bevacizumab has been proposed as treatment option, and the purpose of the current article is to assess the use of intravenous bevacizumab in patients with HHT in 2022 according to available data.     

《邵氏医案》从血辨治痛经浅析

[目的]分析总结浙江近代著名临床医家邵兰荪治疗痛经的经验,以期为临床治疗提供借鉴。[方法]通过研读裘吉生编《邵氏医案》,筛选出其中治疗痛经的医案十余则,并结合邵氏在妇科方面的学术思想,进一步分析其辨证立法遣方特色,从而总结邵氏治疗痛经的临证经验。[结果]邵氏治疗痛经多从血辨治,且分虚实两端,其中属虚者血虚内热用益母胜金丹养血清热、活血止痛,血虚肝风治以养血柔肝、息风止痛;属实者水结血瘀用五苓散利水散瘀、行气止痛,气阻血滞治从行气活血、调经止痛。[结论]在治疗妇人痛经方面,邵氏辨治遣方确有独特经验,这些经验可为中医药治疗此类疾病拓宽诊治思路,有助于提高临床疗效。     

Acquired acrodermatitis enteropathica due to zinc‐depleted parenteral nutrition

Well‐known causes of zinc deficiency, also referred to as acrodermatitis enteropathica (AE), include defects in intestinal zinc transporters and inadequate intake, but a rare cause of acquired zinc deficiency discussed here is an iatrogenic nutritional deficiency caused by parenteral nutrition administered without trace elements. While zinc‐depleted parenteral nutrition causing dermatosis of acquired zinc deficiency was first reported in the 1990s, it is now again relevant due to a national vitamin and trace element shortage. A high index of suspicion may be necessary to diagnose zinc deficiency, particularly because early clinical findings are nonspecific. We present this case of acquired zinc deficiency in a patient admitted to a pediatric intensive care unit for respiratory distress and atypical pneumonia, who subsequently developed a severe bullous eruption due to iatrogenic zinc deficiency but was treated effectively with enteral and parenteral zinc supplementation, allowing for rapid re‐epithelialization of previously denuded skin.