Molecular Genetics and Metabolism Reports最新文献

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Think classical homocystinuria if the genetic test did not confirm Marfan syndrome: Late diagnosis and phenotypic variability in adult siblings with classical homocystinuria 如果基因测试没有证实马凡氏综合征，考虑经典同型半胱氨酸尿：经典同型半胱氨酸尿的成年兄弟姐妹的晚期诊断和表型变异性

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.ymgmr.2025.101261

Randa Sultan , Jordan Urlacher , Taryn Athey , Peter Kannu , Peter Seres , Saadet Mercimek-Andrews

Classical homocystinuria is an inherited metabolic disease of homocysteine metabolism due to biallelic pathogenic variants in CBS. The biochemical hallmark is elevated homocysteine and methionine levels. The treatment consists of betaine supplementation and protein restricted diet. We report two adult siblings with late diagnosis of classical homocystinuria, a variable phenotype and good response to the treatment.

Patient 1 is a 29-year-old female with a history of myopia, Marfanoid habitus with significant kyphoscoliosis, anxiety and a psychotic episode. Clinical exome sequencing identified compound heterozygous pathogenic variants in CBS (c.209+1G>A; c.992C>T (p.Ala331Val)). She had markedly elevated homocysteine (298 μmol/L) and methionine (1040 μmol/L) levels. Her brain magnetic resonance spectroscopy revealed a low n-acetyl-aspartic acid peak. She was started on betaine supplementation, and a protein-restricted diet (0.8 g/kg/day) leading to significant decrease in her homocysteine (37 μmol/L) and methionine (49 μmol/L) levels. Patient 2 is a 27-year-old female (younger sibling) with a history of anxiety, one generalized tonic-clonic seizure and a dural sinus thrombosis in neuroimaging. She had both familial CBS variants and markedly elevated homocysteine (152 μmol/L) and methionine (560 μmol/L) levels, which were improved significantly on betaine supplementation and the protein-restricted diet. Both siblings had average range intellectual abilities. Higher homocysteine levels may result in severe skeletal, and central nervous system phenotypes.

经典同型半胱氨酸尿是由CBS双等位基因致病变异引起的同型半胱氨酸代谢的遗传性代谢性疾病。其生化标志是同型半胱氨酸和蛋氨酸水平升高。治疗包括补充甜菜碱和限制蛋白质饮食。我们报告两名成年兄弟姐妹晚期诊断为经典同型半胱氨酸尿，表型可变，对治疗反应良好。患者1是一名29岁的女性，有近视史，有明显的后凸性脊柱侧凸、焦虑和一次精神病发作。临床外显子组测序鉴定出CBS的复合杂合致病变异（c.209+1G>；A; c.992C>T (p.Ala331Val)）。同型半胱氨酸（298 μmol/L）和蛋氨酸（1040 μmol/L）水平明显升高。她的脑磁共振波谱显示了一个低n-乙酰-天冬氨酸峰。她开始补充甜菜碱，并限制蛋白质饮食（0.8 g/kg/天），导致她的同型半胱氨酸（37 μmol/L）和蛋氨酸（49 μmol/L）水平显著下降。患者2为27岁女性（弟弟妹妹），有焦虑史，一次全身性强直阵挛性发作，神经影像学检查发现硬脑膜窦血栓形成。她有家族性CBS变异，同型半胱氨酸（152 μmol/L）和蛋氨酸（560 μmol/L）水平显著升高，在补充甜菜碱和限制蛋白质饮食后显著改善。兄弟姐妹的智力都处于中等水平。较高的同型半胱氨酸水平可能导致严重的骨骼和中枢神经系统表型。

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引用次数: 0

Siblings of FBXL4-related mitochondrial DNA depletion syndrome, leading to fatal fulminant pneumonia fbxl4相关线粒体DNA缺失综合征的兄弟姐妹，导致致命的暴发性肺炎

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.ymgmr.2025.101266

Takato Akiba , Shino Shimada , Shimpei Matsuda , Shoji Ishida , Yosuke Baba , Atsushi Yamashita , Hiromichi Shoji , Yasushi Okazaki , Kei Murayama

The F-box and leucine-rich repeat protein 4 (FBXL4) is a nuclear encoded mitochondrial protein essential for mitochondrial DNA (mtDNA) maintenance. Biallelic variants in FBXL4 cause FBXL4-related mitochondrial DNA depletion syndrome (FBXL4-MTDPS), characterized by lactic acidosis and developmental delay. We report two siblings diagnosed with FBXL4-MTDPS who died of fulminant pneumonia in infancy; autopsy revealed extensive pulmonary inflammation consistent with severe bacterial infection. FBXL4-MTDPS may involve intrinsic defects in pulmonary infection defense, increasing susceptibility to fatal infection such as pneumonia.

F-box和富含亮氨酸的重复蛋白4 （FBXL4）是线粒体DNA （mtDNA）维持所必需的核编码线粒体蛋白。FBXL4双等位基因变异导致FBXL4相关线粒体DNA缺失综合征（FBXL4- mtdps），其特征是乳酸酸中毒和发育迟缓。我们报告了两个被诊断为FBXL4-MTDPS的兄弟姐妹，他们在婴儿期死于暴发性肺炎；尸检显示广泛的肺部炎症与严重的细菌感染一致。FBXL4-MTDPS可能涉及肺部感染防御的内在缺陷，增加对肺炎等致命感染的易感性。

引用次数: 0

Long-term neuromuscular, cardiac and liver outcomes in an adult man affected with Chanarin-Dorfman syndrome 成年男性Chanarin-Dorfman综合征的长期神经肌肉、心脏和肝脏预后

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-10-07 DOI: 10.1016/j.ymgmr.2025.101265

Kinza Noman , Andreas Tridimas , James B. Lilleker , Gaetano Nucifora , Peter Woolfson , Daniel du Plessis , Alison Woodall , Andrew Oldham , Mark E. Roberts , John Bassett , Federico Roncaroli , Simon A. Jones , Stefan Coassin , Florian Kronenberg , Karolina M. Stepien

Chanarin-Dorfman syndrome (CDS) is an ultra-rare autosomal recessive subtype of neutral lipid storage disorder (NLSD); it is characterised by ichthyosis and intracytoplasmic accumulation of lipid droplets containing triglycerides, most commonly in granulocytes, muscle fibres, skin and liver. Several pathogenic variants in the ABHD5/CGI-58 gene have been described. Clinical manifestations include steatohepatitis, myopathy, ophthalmic disease, developmental delay. Liver involvement is an important cause of morbidity and mortality.

We present a case of a 26-year-old male diagnosed with ichthyotic NLSD in childhood, who developed progressive myopathy and cardiac fibrosis in adulthood. He was treated with a combination of low-fat diet, MCT oil and co-enzyme Q10 which resulted in an initial improvement in muscle strength and stabilisation of muscle symptoms and well-being.

Synopsis: Medical and dietetic management of liver and muscle complications in Chanarin-Dorfman syndrome.

Chanarin-Dorfman综合征（CDS）是一种超罕见的常染色体隐性中性脂质储存障碍（NLSD）亚型；其特征是鱼鳞病和含有甘油三酯的脂滴在胞浆内积聚，最常见于粒细胞、肌纤维、皮肤和肝脏。已经描述了ABHD5/CGI-58基因的几种致病变异。临床表现包括脂肪性肝炎、肌病、眼疾、发育迟缓。肝脏受累是发病和死亡的重要原因。我们报告了一个26岁的男性在儿童期被诊断为鱼鳞病性NLSD，在成年期发展为进行性肌病和心脏纤维化。患者接受低脂饮食、MCT油和辅酶Q10联合治疗，肌肉力量得到初步改善，肌肉症状和健康状况得到稳定。摘要：Chanarin-Dorfman综合征肝脏和肌肉并发症的医学和饮食管理。

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引用次数: 0

Carbonic anhydrase VA deficiency due to a novel CA5A variant 一种新的CA5A变异引起的碳酸酐酶VA缺乏

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-10-04 DOI: 10.1016/j.ymgmr.2025.101259

Laura Keehan , Elizabeth Null , Lekha Chilakamarri , Christopher Carter , Chung Lee , Gregory M. Enns , Dena R. Matalon

Carbonic anhydrase VA (CA-VA) deficiency is a rare autosomal recessive inborn error of metabolism characterized by variable neonatal onset metabolic acidosis, hyperammonemia, lactic acidosis, and ketonuria. To date, there have been 41 cases of CA-VA deficiency described in the literature. Here, we report the clinical history and biochemical laboratory findings of a newborn female with a novel homozygous missense variant in CA5A. This case adds to the literature of biochemical findings and ancestral diversity in individuals with CA-VA deficiency.

碳酸酐酶VA （CA-VA）缺乏症是一种罕见的常染色体隐性先天性代谢错误，其特征是新生儿发生变异性代谢性酸中毒、高氨血症、乳酸酸中毒和酮症尿。迄今为止，文献中已有41例CA-VA缺乏症。在这里，我们报告了一名新生女性的CA5A纯合错义变异的临床病史和生化实验室结果。本病例增加了文献中的生物化学发现和CA-VA缺乏症个体的祖先多样性。

引用次数: 0

Risk of inadequate protein and micronutrient intakes in patients with PKU with an increased phe-tolerance: Impact of a micronutrient-dense protein substitute 对ph耐受性增加的PKU患者蛋白质和微量营养素摄入不足的风险：微量营养素密集蛋白质替代品的影响

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-10-04 DOI: 10.1016/j.ymgmr.2025.101264

Carmen Rohde , Denise Leonne Hofman , Ira Klawon , Frank Rutsch , Iris Rodenburg , Francjan van Spronsen , Alena Gerlinde Thiele , Willie Woestenenk , Skadi Beblo

Background

Patients with phenylketonuria (PKU) with higher phenylalanine (phe)-tolerance may have inadequate diets due to high-quality protein restriction and reduced intakes of nutrient-fortified phe-free, tyrosine (tyr)-enriched protein substitutes (PS).

Methods

Open-label, 24-week, multi-centre intervention assessed the impact of a once-daily, micronutrient-dense PS on nutrient intakes in patients with an increased phe-tolerance. Subjects >12 years, consuming 0–25 g protein/day from a regular PS, were recruited. Diet records and fasting blood samples were collected at baseline and study end.

Results

11/13 subjects, 15-49y (5 males), with 6/11 taking tetrahydrobiopterin dihydrochloride (BH4) and/or a regular PS, completed the study. At baseline, protein and some essential amino acids (EAA) intakes were below recommendations in 4/11 and 3/11 subjects, respectively. Vitamins A, B2, B12, D, calcium, iron, iodine, zinc and magnesium intakes were below recommendations for 7/11. After the intervention, 2/11 had total protein intakes below recommendations, while 11/11 met EAA recommendations. Micronutrient intakes improved to ≥90 % of recommendations for all subjects except for vitamin B12 (4/11) and phosphorus (1/6). Docosahexaenoic acid (DHA) intakes increased. Blood phe levels remained stable.

Conclusion

Patients with PKU who have relaxed their phe-restricted diet are at risk of insufficient nutrient supply, and dietary counselling should be offered. Consuming the study PS increased nutrient intakes closer to dietary recommendations.

背景：苯丙酮尿症（PKU）患者对苯丙氨酸（phe）耐受性较高，由于限制高质量蛋白质和减少营养强化的不含苯丙氨酸、酪氨酸（tyr）丰富的蛋白质替代品（PS）的摄入，PKU患者可能饮食不足。方法：开放标签、24周、多中心干预评估每日一次、微量营养素密集PS对ph耐受性增加的患者营养摄入的影响。研究招募了12岁的受试者，每天从普通PS中摄取0-25克蛋白质。在基线和研究结束时收集饮食记录和空腹血液样本。结果11/13名受试者（15-49岁，男性5名）完成了研究，其中6/11人服用了盐酸四氢生物蝶呤（BH4）和/或常规PS。在基线时，4/11和3/11受试者的蛋白质和一些必需氨基酸（EAA）摄入量分别低于推荐值。维生素A、B2、B12、D、钙、铁、碘、锌和镁的摄入量低于7月11日的建议摄入量。干预后，2/11的总蛋白质摄入量低于推荐值，11/11的总蛋白质摄入量达到EAA推荐值。除维生素B12（4/11）和磷（1/6）外，所有受试者的微量营养素摄入量均提高至推荐摄入量的90%以上。二十二碳六烯酸（DHA）的摄入量增加。血液phe水平保持稳定。结论放松限磷饮食的PKU患者存在营养供应不足的风险，应进行饮食咨询。食用研究PS增加的营养摄入量更接近膳食建议。

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引用次数: 0

Insights into ALG3-CDG: A case study combining glycan profiling and genetic analysis 对ALG3-CDG的见解：一个结合聚糖谱和遗传分析的案例研究

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-09-30 DOI: 10.1016/j.ymgmr.2025.101263

Rebeka Kodríková , Zuzana Pakanová , Maroš Krchňák , Veronika Krajčovičová , Anna Šalingová , Katarína Skalická , Miriam Kolníková , Peter Baráth , Marek Nemčovič

Congenital disorders of glycosylation (CDG) are a group of rare metabolic disorders caused by the defects in the glycosylation pathways of biomacromolecules leading to altered glycoprofiles in affected individuals. In this case study, we present a 3-year-old Slovak male patient with developmental delay, hearing impairment, epilepsy, microcephaly, facial dysmorphism, corpus callosum dysgenesis, and cardiac abnormalities. To elucidate the underlying cause, we performed LC-ESI-MS analysis of RapiFluor-labelled N-glycans released from blood serum glycoproteins. The results revealed an abnormal N-glycan profile, characterized by an increased relative abundance of truncated mannosylated structures (Hex3HexNAc2 and Hex4HexNAc2) and a decreased presence of higher-order mannose structures (Hex6-8HexNAc2). A molecular analysis was also conducted. Whole exome sequencing confirmed a diagnosis of ALG3-CDG with compound heterozygous variants: c.165C > T (p.Gly55=) and c.1060C > T (p.Arg354Cys) in the ALG3 gene, encoding alpha-1,3-mannosyltransferase in the endoplasmic reticulum. This presented case highlights the importance of glycan profiling and genetic analysis in diagnosing congenital disorders of glycosylation, facilitating early intervention and management.

先天性糖基化障碍（Congenital disorders of glycosylation， CDG）是一组罕见的代谢性疾病，是由生物大分子糖基化途径缺陷导致患者糖谱改变而引起的。在这个案例研究中，我们提出了一个3岁的斯洛伐克男性患者发育迟缓，听力障碍，癫痫，小头畸形，面部畸形，胼胝体发育不良和心脏异常。为了阐明潜在的原因，我们对从血清糖蛋白中释放的rapifluor标记的n -聚糖进行了LC-ESI-MS分析。结果显示n -聚糖谱异常，其特征是截断甘露糖基化结构（Hex3HexNAc2和Hex4HexNAc2）的相对丰度增加，而高阶甘露糖结构（Hex6-8HexNAc2）的存在减少。并进行了分子分析。全外显子组测序证实ALG3- cdg具有复合杂合变异体：编码内质网α -1,3-甘露糖基转移酶的ALG3基因中的c.165C > T （p.Gly55=）和c.1060C > T （p.Arg354Cys）。本病例强调了糖基化先天性疾病诊断中糖基化分析和基因分析的重要性，促进了早期干预和管理。

{"title":"Insights into ALG3-CDG: A case study combining glycan profiling and genetic analysis","authors":"Rebeka Kodríková , Zuzana Pakanová , Maroš Krchňák , Veronika Krajčovičová , Anna Šalingová , Katarína Skalická , Miriam Kolníková , Peter Baráth , Marek Nemčovič","doi":"10.1016/j.ymgmr.2025.101263","DOIUrl":"10.1016/j.ymgmr.2025.101263","url":null,"abstract":"<div><div>Congenital disorders of glycosylation (CDG) are a group of rare metabolic disorders caused by the defects in the glycosylation pathways of biomacromolecules leading to altered glycoprofiles in affected individuals. In this case study, we present a 3-year-old Slovak male patient with developmental delay, hearing impairment, epilepsy, microcephaly, facial dysmorphism, corpus callosum dysgenesis, and cardiac abnormalities. To elucidate the underlying cause, we performed LC-ESI-MS analysis of RapiFluor-labelled <em>N-</em>glycans released from blood serum glycoproteins. The results revealed an abnormal <em>N</em>-glycan profile, characterized by an increased relative abundance of truncated mannosylated structures (Hex3HexNAc2 and Hex4HexNAc2) and a decreased presence of higher-order mannose structures (Hex6-8HexNAc2). A molecular analysis was also conducted. Whole exome sequencing confirmed a diagnosis of ALG3-CDG with compound heterozygous variants: c.165C > T (p.Gly55=) and c.1060C > T (p.Arg354Cys) in the <em>ALG3</em> gene, encoding alpha-1,3-mannosyltransferase in the endoplasmic reticulum. This presented case highlights the importance of glycan profiling and genetic analysis in diagnosing congenital disorders of glycosylation, facilitating early intervention and management.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101263"},"PeriodicalIF":1.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Case report: Lysine improvement in siblings with glutaric acidemia type 1 following reduced medical food intake: Implications for amino acid absorption and reabsorption 病例报告：减少医疗食品摄入后1型戊二酸血症兄弟姐妹赖氨酸改善：对氨基酸吸收和再吸收的影响

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-09-29 DOI: 10.1016/j.ymgmr.2025.101262

Grace Noh , Jariya Upadia

Glutaric acidemia type 1 (GA1) is a rare metabolic disorder requiring dietary management with lysine (Lys)-free, tryptophan (Trp)-reduced, and arginine (Arg)-fortified medical formulas. This case report describes three siblings with GA1 who exhibited persistently low plasma lysine levels despite meeting age-appropriate dietary protein intake from intact protein sources. Upon reducing medical formula intake while maintaining intact protein consumption, lysine levels normalized, suggesting that excess dietary arginine may inhibit lysine intestinal uptake or reabsorption in the kidneys. These findings highlight the need for further research on amino acid interactions in GA1 dietary management and emphasize careful formula prescription to prevent unintended lysine deficiency.

1型戊二酸血症（GA1）是一种罕见的代谢性疾病，需要使用不含赖氨酸（Lys）、减少色氨酸（Trp）和强化精氨酸（Arg）的医疗配方进行饮食管理。本病例报告描述了三个患有GA1的兄弟姐妹，尽管他们从完整的蛋白质来源中摄入了与年龄相适应的膳食蛋白质，但他们的血浆赖氨酸水平持续较低。在减少药物配方摄入量的同时保持完整的蛋白质消耗，赖氨酸水平恢复正常，这表明过量的膳食精氨酸可能抑制赖氨酸在肠道的吸收或肾脏的再吸收。这些发现强调了进一步研究氨基酸相互作用在GA1饮食管理中的必要性，并强调了谨慎的配方处方以防止意外的赖氨酸缺乏。

引用次数: 0

Molecular characterization of a novel synonymous variant in a Mexican patient with Pompe disease 墨西哥庞贝病患者一种新型同义变异的分子特征

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-09-27 DOI: 10.1016/j.ymgmr.2025.101253

Carmen Alaez-Verson , Carlos Alberto González-Domínguez , Imelda Vergara Sanchez , Luz María Sanchez Sanchez , Ivonne Natalia Flores , Ekaterina Kazakova , Joaquin Garcia-Solorio , Carolina Molina-Garay , Luis Leonardo Flores-Lagunes , Ivan Martínez Duncker

Introduction

Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-1,4-glucosidase (GAA; EC 3.2.1.20), encoded by the GAA gene, leading to progressive neuromuscular deterioration. The mutational spectrum of GAA is expanding, particularly with recognition of splicing-impacting synonymous variants. Here, we report the molecular characterization and reclassification of a novel synonymous GAA variant in a female Mexican patient with enzymatically confirmed infantile-onset PD (IOPD).

Methods

DNA and RNA were extracted from peripheral blood. Next-generation sequencing of a clinical exome panel identified variants in the GAA gene. The whole coding sequence of the GAA was amplified from cDNA, subcloned, and analyzed by Sanger sequencing to assess splicing alterations.

Results

The pathogenic variant c.1979G > A (p.Arg660His) and a novel VUS c.2799G > A (p.Lys933=) were detected. The variant c.2799G > A is predicted to affect splicing. mRNA analysis revealed three isoforms, one corresponding to c.1979G > A and two others caused by alternative splicing of c.2799G > A (isoforms 1 and 2). The isoform-1 showed c.2799G > A, followed by 61 bp retention of intron 19, predicted to cause a frameshift p.(A934fs). Isoform 2 has a 90 bp deletion in exon 19, resulting in a p.V904_K933del in-frame deletion.

Discussion

This study demonstrates that the synonymous variant c.2799G > A is pathogenic due to its impact on RNA splicing. Our findings highlight the importance of transcript analysis for VUS reclassification and stress the clinical relevance of evaluating synonymous variants in genetic diagnostics and patient management.

pompe病（PD）是一种常染色体隐性遗传病，由GAA基因编码的溶酶体酸α -1,4-葡萄糖苷酶（GAA; EC 3.2.1.20）缺乏引起，导致进行性神经肌肉恶化。GAA的突变谱正在扩大，特别是随着对剪接影响的同义变体的识别。在这里，我们报告了一种新的同义GAA变异体的分子特征和重新分类，该变异体出现在一名墨西哥女性患者中，酶确证为婴儿期PD （IOPD）。方法提取外周血dna和RNA。下一代临床外显子组测序鉴定出GAA基因的变异。从cDNA中扩增GAA的整个编码序列，进行亚克隆，并通过Sanger测序分析剪接变化。结果检出致病性变异株c.1979G > A （p.Arg660His）和新型毒株c.2799G > A （p.Lys933=）。预计c.2799G >； A的变体会影响剪接。mRNA分析显示了三个亚型，一个对应于c.1979G >； A，另外两个由c.2799G >； A的可变剪接引起（亚型1和2）。异构体1显示c.2799G >； A，内含子19保留61 bp，预计会引起移码p.（A934fs）。同种异构体2外显子19缺失90 bp，导致p.V904_K933del帧内缺失。本研究表明同义变异体c.2799G >； A由于其对RNA剪接的影响而具有致病性。我们的研究结果强调了转录分析对VUS重新分类的重要性，并强调了在遗传诊断和患者管理中评估同义变异体的临床相关性。

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引用次数: 0

Case report of neuronopathic mucopolysaccharidosis type II: Early intracerebroventricular enzyme replacement therapy and hematopoietic cell transplantation with developmental outcomes up to 5 years of age 神经性粘多糖病II型病例报告：早期脑室内酶替代治疗和造血细胞移植，发育结局可达5岁

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-09-25 DOI: 10.1016/j.ymgmr.2025.101254

Azuma Ikari , Asahito Hama , Torayuki Okuyama

Neuronopathic mucopolysaccharidosis type II (MPS II) is a severe lysosomal storage disorder associated with early-onset developmental regression and a poor prognosis. Although enzyme replacement therapy (ERT) and hematopoietic cell transplantation (HCT) have been employed to address systemic symptoms, they have not demonstrated sufficient efficacy in treating central nervous system (CNS) involvement. The intracerebroventricular administration of idursulfase beta has emerged as a novel approach for targeting CNS manifestations. Here, we report the clinical course of a male patient diagnosed with neuronopathic MPS II at 2 months of age, based on family history and genetic analysis. Intravenous ERT was initiated early, followed by the introduction of intracerebroventricular idursulfase beta at 10 months, and HCT at 23 months. Since then, only intracerebroventricular ERT has been continued. At 5 years of age, the patient exhibited age-appropriate neurodevelopment, stable cognitive function, and normal physical growth without signs of developmental regression. Imaging findings remained stable, and cerebrospinal fluid biomarkers normalized. Notably, the patient harbored a missense variant potentially associated with residual enzymatic activity, which may have contributed to favorable outcomes. To our knowledge, this is the first reported case in which normal development was maintained until 5 years of age in a patient with neuronopathic MPS II. This case highlights the potential benefits of early diagnosis and a multimodal therapeutic strategy, including intracerebroventricular ERT and HCT, for preserving neurodevelopment. It also holds significance as a rare but valuable example, suggesting the efficacy of a novel treatment paradigm for a condition traditionally associated with a poor prognosis.

神经性粘多糖病II型（MPS II）是一种严重的溶酶体贮积症，与早发性发育倒退和预后不良有关。虽然酶替代疗法（ERT）和造血细胞移植（HCT）已被用于解决全身性症状，但它们在治疗中枢神经系统（CNS）受累方面尚未显示出足够的疗效。脑室内给药idursulase β已成为一种针对中枢神经系统表现的新方法。在这里，我们报告一名2个月大的男性患者，根据家族史和遗传分析，被诊断为神经性MPS II的临床过程。静脉ERT早期开始，随后在10个月时引入脑室内idursulase β，在23个月时引入HCT。此后，仅继续进行脑室内ERT。5岁时，患者表现出与年龄相适应的神经发育、稳定的认知功能和正常的身体生长，无发育倒退迹象。成像结果保持稳定，脑脊液生物标志物恢复正常。值得注意的是，患者携带一种可能与残留酶活性相关的错义变体，这可能促成了有利的结果。据我们所知，这是首次报道的神经病变MPS II患者正常发育维持到5岁的病例。该病例强调了早期诊断和多模式治疗策略的潜在益处，包括脑室内ERT和HCT，以保护神经发育。作为一个罕见但有价值的例子，它也具有重要意义，表明一种新的治疗模式对传统上与预后不良相关的疾病的疗效。

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引用次数: 0

Real-world experience of switching to taliglucerase among patients with Gaucher disease in Québec: A case series 戈谢病患者改用塔利格卢酶的现实世界经验：一个病例系列

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-09-24 DOI: 10.1016/j.ymgmr.2025.101257

Angelo Rizzolo , Marie-Claude Miron , Jean-François Delisle , Nathalie Alos , Philippe M. Campeau , François Mercier

Enzyme replacement therapy (ERT) for Gaucher disease (GD) effectively prevents skeletal, visceral, and hematologic complications of this inherited, lysosomal storage disorder. Taliglucerase is one of the three commercially available ERT products and became the recommended first-line therapy in Québec, Canada in 2016. Thus, 19 patients were switched from imiglucerase to taliglucerase, but more than a quarter experienced significant side effects. Here, we summarize these patients' clinical course and describe 6 suspected product-related adverse-effects.

戈谢病（GD）的酶替代疗法（ERT）有效地预防了这种遗传性溶酶体贮积疾病的骨骼、内脏和血液学并发症。Taliglucerase是三种市售ERT产品之一，并于2016年成为加拿大qu忧郁省推荐的一线治疗药物。因此，19名患者从伊米格鲁酶转为塔利格鲁酶，但超过四分之一的患者出现了明显的副作用。在这里，我们总结了这些患者的临床过程，并描述了6个疑似产品相关的不良反应。

引用次数: 0

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