Molecular Genetics and Metabolism Reports最新文献

Unveiling alpha-mannosidosis in Iraqi children: A series of clinically and genetically characterized cases with novel MAN2B1 variant 揭示伊拉克儿童α -甘露甘露病：一系列具有新型MAN2B1变异的临床和遗传特征的病例

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2026-01-09 DOI: 10.1016/j.ymgmr.2025.101282

Mays Riyadh Al Tai , Nebal Waill Saadi , Marwa Sabah Alothman , Ikhlas Ali Ahmed , Hala Sameh Arif , Saja Baheer Abdulwahhab

Background

Alpha-mannosidosis is a rare lysosomal storage disorder caused by MAN2B1 mutations, leading to cognitive decline, hearing loss, infections, and skeletal abnormalities. Limited data exist from the Middle East; this study describes the clinical and genetic features of affected Iraqi children.

Patients and methods

This study was conducted at Children Welfare Teaching Hospital, and Al Emamayn Al Khadimiyan Medical City Baghdad, Iraq. We retrospectively reviewed children diagnosed with alpha-mannosidosis (2017–2025). Diagnosis was confirmed by enzyme assay and MAN2B1 testing. Clinical and imaging data were collected from medical records.

Results

A total of nine children from five unrelated families were identified. The cohort included seven males and two females. The mean age at symptoms onset was 1.1 ± 0.5 years, while the mean age at diagnosis was 10.7 ± 7.6 years, indicating a diagnostic delay of approximately 9.6 ± 7.4 years. All the patients were born to consanguineous parents. The most common clinical features included psychomotor delay, sensorineural hearing loss and coarse facial features (100 % for each). Neuroimaging of the brain revealed variable findings, and skeletal radiographs showed dysostosis multiplex in 4/9 patients. Genetic testing revealed three pathogenic/likely pathogenic MAN2B1 variants, including one novel variant [c.830C > T (p.Pro277Leu)].

Conclusion

Our findings represent the first clinical and molecular characterization of alpha-mannosidosis in Iraqi children and reveal previously unreported genetic features in this population. It highlights that clinical and laboratory findings in our patients were largely consistent with previously published regional and international data. It demonstrates notable diagnostic delay and identified novel variants, expanding the mutational spectrum associated with the disease.

甘露甘露病是一种罕见的由MAN2B1突变引起的溶酶体贮积疾病，可导致认知能力下降、听力丧失、感染和骨骼异常。来自中东的数据有限；这项研究描述了受影响的伊拉克儿童的临床和遗传特征。患者和方法本研究在伊拉克巴格达的儿童福利教学医院和Al Emamayn Al Khadimiyan医疗城进行。我们回顾性分析了2017-2025年诊断为α -甘露酸菌病的儿童。通过酶分析和MAN2B1检测确诊。临床和影像学资料收集自医疗记录。结果共鉴定出来自5个无血缘关系家庭的9名儿童。该队列包括7名男性和2名女性。出现症状时的平均年龄为1.1±0.5岁，而诊断时的平均年龄为10.7±7.6岁，表明诊断延迟约9.6±7.4年。所有病人的父母都是近亲。最常见的临床特征包括精神运动性延迟、感音神经性听力损失和粗糙的面部特征（每项100%）。脑神经影像学显示不同的结果，骨骼x线片显示4/9的患者多发性骨缺损。基因检测发现三种致病/可能致病的MAN2B1变异，包括一种新变异[c]。[qh] [p]；结论：我们的研究结果代表了伊拉克儿童α -甘露甘露病的第一个临床和分子特征，并揭示了该人群中以前未报道的遗传特征。它强调，我们患者的临床和实验室结果与以前发表的区域和国际数据基本一致。它显示了显著的诊断延迟和识别新的变异，扩大了与疾病相关的突变谱。

{"title":"Unveiling alpha-mannosidosis in Iraqi children: A series of clinically and genetically characterized cases with novel MAN2B1 variant","authors":"Mays Riyadh Al Tai , Nebal Waill Saadi , Marwa Sabah Alothman , Ikhlas Ali Ahmed , Hala Sameh Arif , Saja Baheer Abdulwahhab","doi":"10.1016/j.ymgmr.2025.101282","DOIUrl":"10.1016/j.ymgmr.2025.101282","url":null,"abstract":"<div><h3>Background</h3><div>Alpha-mannosidosis is a rare lysosomal storage disorder caused by <em>MAN2B1</em> mutations, leading to cognitive decline, hearing loss, infections, and skeletal abnormalities. Limited data exist from the Middle East; this study describes the clinical and genetic features of affected Iraqi children.</div></div><div><h3>Patients and methods</h3><div>This study was conducted at Children Welfare Teaching Hospital, and Al Emamayn Al Khadimiyan Medical City Baghdad, Iraq. We retrospectively reviewed children diagnosed with alpha-mannosidosis (2017–2025). Diagnosis was confirmed by enzyme assay and <em>MAN2B1</em> testing. Clinical and imaging data were collected from medical records.</div></div><div><h3>Results</h3><div>A total of nine children from five unrelated families were identified. The cohort included seven males and two females. The mean age at symptoms onset was 1.1 ± 0.5 years, while the mean age at diagnosis was 10.7 ± 7.6 years, indicating a diagnostic delay of approximately 9.6 ± 7.4 years. All the patients were born to consanguineous parents. The most common clinical features included psychomotor delay, sensorineural hearing loss and coarse facial features (100 % for each). Neuroimaging of the brain revealed variable findings, and skeletal radiographs showed dysostosis multiplex in 4/9 patients. Genetic testing revealed three pathogenic/likely pathogenic <em>MAN2B1</em> variants, including one novel variant [c.830C > T (p.Pro277Leu)].</div></div><div><h3>Conclusion</h3><div>Our findings represent the first clinical and molecular characterization of alpha-mannosidosis in Iraqi children and reveal previously unreported genetic features in this population. It highlights that clinical and laboratory findings in our patients were largely consistent with previously published regional and international data. It demonstrates notable diagnostic delay and identified novel variants, expanding the mutational spectrum associated with the disease.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101282"},"PeriodicalIF":1.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929217","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

Molecular characterization of Alkaptonuria in Brazilian patients 巴西患者尿酸钠的分子特征

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2026-01-06 DOI: 10.1016/j.ymgmr.2025.101288

Carolina Araújo Moreno , Ruy Pires de Oliveira Sobrinho , Josep Jorente , Simone Appenzeller , Nelma Gláucia Silva Meira , Lucas Cadete Caldeira Costa , Angelina Xavier Acosta , The Brazilian Rare Genomes Project Consortium , Mara Sanches Guaragna , Carlos Eduardo Steiner

Objective

Alkaptonuria is a rare inborn error of metabolism, with few reports from Brazil and typically lacking genotype descriptions in the Brazilian population.

Methods

A retrospective study of clinical and molecular data of individuals with alkaptonuria submitted to whole genome sequencing.

Results

Five individuals from four unrelated families were enrolled, with ages ranging from 8 months to 61 years at first evaluation and currently ranging from 26 to 65 years. All presented a history of dark urine since infancy and accentuated elevation of homogentisic acid excretion in urine samples. In two consanguineous families from the State of Bahia, the c.847 A > T and c.899 T > G variants were identified in homozygous status in the HGD gene; one of the individuals also had a history of infertility and presented the homozygous c.537 + 1G > A variant in the STX2 gene. The two remaining families without consanguinity, both from the State of São Paulo, presented with a combination of the heterozygous variants c.508G > A and c.899 T > G in one individual, and deletion of exon 13 of the HGD gene in trans with the c.1007-172 A > G deep intronic variant as a possible causative variant in another patient.

Conclusions

Although small, the present series represents the first cohort of Brazilian individuals with alkaptonuria investigated by genomic sequencing, identifying a common variant (c.899 T > G) in two families and three exonic and one deep intronic variant in the HGD gene, besides a possible double diagnosis comprising infertility due to a homozygous variant of uncertain significance in the STX2 gene.

目的尿酸钠是一种罕见的先天性代谢错误，在巴西很少有报道，在巴西人群中通常缺乏基因型描述。方法采用全基因组测序方法对尿酸尿患者的临床和分子资料进行回顾性分析。结果入选的5例患者来自4个无血缘关系的家庭，首次评估时年龄为8个月~ 61岁，目前年龄为26 ~ 65岁。所有患者均表现为婴儿期以来尿色深，尿样均质酸排泄增高。在巴伊亚州的两个近亲家庭中，公元847年A >； T和c.899在HGD基因中发现了纯合状态的T >； G变异；其中1例患者有不育史，STX2基因为c.537 + 1G >； a纯合子变异。其余两个无血缘关系的家庭，均来自圣保罗州，表现出c.508G >； a和c.899的杂合变异组合在另一名患者中，c.1007-172 A >； G深内含子变异的HGD基因13外显子缺失可能是一种致病变异。结论：虽然规模很小，但本系列研究是巴西首例尿酸尿患者基因组测序研究，发现了一种常见变异（c.899）T >； G)在两个家族和HGD基因的三个外显子和一个深内含子变异，除了可能的双重诊断包括不孕不育由于STX2基因的纯合子变异的不确定意义。

{"title":"Molecular characterization of Alkaptonuria in Brazilian patients","authors":"Carolina Araújo Moreno , Ruy Pires de Oliveira Sobrinho , Josep Jorente , Simone Appenzeller , Nelma Gláucia Silva Meira , Lucas Cadete Caldeira Costa , Angelina Xavier Acosta , The Brazilian Rare Genomes Project Consortium , Mara Sanches Guaragna , Carlos Eduardo Steiner","doi":"10.1016/j.ymgmr.2025.101288","DOIUrl":"10.1016/j.ymgmr.2025.101288","url":null,"abstract":"<div><h3>Objective</h3><div>Alkaptonuria is a rare inborn error of metabolism, with few reports from Brazil and typically lacking genotype descriptions in the Brazilian population.</div></div><div><h3>Methods</h3><div>A retrospective study of clinical and molecular data of individuals with alkaptonuria submitted to whole genome sequencing.</div></div><div><h3>Results</h3><div>Five individuals from four unrelated families were enrolled, with ages ranging from 8 months to 61 years at first evaluation and currently ranging from 26 to 65 years. All presented a history of dark urine since infancy and accentuated elevation of homogentisic acid excretion in urine samples. In two consanguineous families from the State of Bahia, the c.847 A > T and c.899 T > G variants were identified in homozygous status in the <em>HGD</em> gene; one of the individuals also had a history of infertility and presented the homozygous c.537 + 1G > A variant in the <em>STX2</em> gene. The two remaining families without consanguinity, both from the State of São Paulo, presented with a combination of the heterozygous variants c.508G > A and c.899 T > G in one individual, and deletion of exon 13 of the <em>HGD</em> gene in trans with the c.1007-172 A > G deep intronic variant as a possible causative variant in another patient.</div></div><div><h3>Conclusions</h3><div>Although small, the present series represents the first cohort of Brazilian individuals with alkaptonuria investigated by genomic sequencing, identifying a common variant (c.899 T > G) in two families and three exonic and one deep intronic variant in the <em>HGD</em> gene, besides a possible double diagnosis comprising infertility due to a homozygous variant of uncertain significance in the <em>STX2</em> gene.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101288"},"PeriodicalIF":1.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897978","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

Identification of Multiple Sulfatase Deficiency (MSD) in newborn screening: A case study 在新生儿筛查中识别多重磺胺脂酶缺乏症（MSD）：一个案例研究

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2026-01-06 DOI: 10.1016/j.ymgmr.2025.101285

Taraka R. Donti, James C. DiPerna, Madhuri R. Hegde, Revvity Omics, Inc

A patient with multiple sulfatase deficiency (MSD) was identified through a lysosomal storage disorder enzyme analysis panel, based on a characteristic pattern of reduced activities across multiple sulfatases. Newborn screening laboratories implement various quality control protocols to assess the integrity of received samples. The quality control policy for identifying heat-denatured samples evaluates several enzyme activity levels to determine if a sample has been compromised by excessive heat. A new quality control policy has been established to differentiate heat-denatured samples from those affected by Multiple Sulfatase Deficiency.

通过溶酶体储存障碍酶分析小组，根据多种硫酸酯酶活性降低的特征模式，确定了多发性硫酸酯酶缺乏症（MSD）患者。新生儿筛查实验室实施各种质量控制方案，以评估收到的样本的完整性。鉴定热变性样品的质量控制政策评估几种酶活性水平，以确定样品是否因过热而受损。建立了一种新的质量控制政策，以区分热变性样品和多种硫酸盐酶缺乏症样品。

引用次数: 0

Biochemical characterization of the FH variant p.Lys414Glu reveals loss of enzymatic function and disrupted multimerization FH变体p.Lys414Glu的生化特性揭示了酶功能的丧失和多聚性的破坏

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2026-01-06 DOI: 10.1016/j.ymgmr.2025.101287

Connor J. Huck , Isabella Devaprasad , Blake R. Wilde

Variants of uncertain significance (VUS) in fumarate hydratase (FH) complicate the diagnosis of hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH VUS p.Lys414Glu has been reported in patients with HLRCC features but additional evidence is needed to support an interpretation of pathogenicity. Here we show that p.Lys414Glu is completely inactive, supporting a classification of pathogenic and providing critical evidence for clinical care and surveillance of patients with germline FH p.Lys414Glu.

富马酸水合酶（FH）的不确定意义变异（VUS）使遗传性平滑肌瘤病和肾细胞癌（HLRCC）的诊断复杂化。FH VUS p.Lys414Glu在具有HLRCC特征的患者中有报道，但需要额外的证据来支持对致病性的解释。本研究显示p.Lys414Glu完全失活，支持病原分类，并为种系FH p.Lys414Glu患者的临床护理和监测提供关键证据。

引用次数: 0

First reported case of adult-onset very long-chain acyl-coa dehydrogenase (vlcad) deficiency in Vietnam: a rare metabolic myopathy 越南首次报道成人发病的甚长链酰基辅酶a脱氢酶（vlcad）缺乏症：一种罕见的代谢性肌病

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2026-01-06 DOI: 10.1016/j.ymgmr.2025.101286

Vinh Phuc Kieu , Thang Van Viet Nguyen , Anh Duc Vu

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare genetic metabolic disorder involving impaired fatty acid β-oxidation. It is caused by mutations in the Acyl-CoA Dehydrogenase Very Long Chain (ACADVL) gene, which encodes the VLCAD enzyme. The clinical presentation is diverse, ranging from a severe neonatal-onset form to a milder adult-onset form. We describe the first reported case in Vietnam, which is a 20-year-old man who presented with exercise intolerance, myalgia, and recurrent rhabdomyolysis triggered by fasting and exertion. Acylcarnitine profiling suggested a fatty acid oxidation disorder, and whole-exome sequencing identified the diagnosis of VLCAD deficiency with c747G > T (p.Trp249Cys) mutation. It has not previously been reported in the Vietnamese population. This case highlights the important role of neonatal screening and genetic testing in the early diagnosis of metabolic myopathies. In addition, it raises awareness of genetic disorders among healthcare providers and the public in developing countries.

甚长链酰基辅酶a脱氢酶（VLCAD）缺乏症是一种罕见的遗传性代谢疾病，涉及脂肪酸β氧化受损。它是由编码VLCAD酶的酰基辅酶a脱氢酶长链（ACADVL）基因突变引起的。临床表现多种多样，从新生儿发病的严重形式到成人发病的轻微形式。我们描述了越南的第一例报告病例，这是一名20岁的男性，他表现为运动不耐受、肌痛和由禁食和运动引发的复发性横纹肌溶解。酰基肉碱分析提示脂肪酸氧化障碍，全外显子组测序确定了c747G >； T （p.Trp249Cys）突变的VLCAD缺陷诊断。以前没有在越南人群中报道过。本病例强调了新生儿筛查和基因检测在代谢性肌病早期诊断中的重要作用。此外，它还提高了发展中国家卫生保健提供者和公众对遗传疾病的认识。

{"title":"First reported case of adult-onset very long-chain acyl-coa dehydrogenase (vlcad) deficiency in Vietnam: a rare metabolic myopathy","authors":"Vinh Phuc Kieu , Thang Van Viet Nguyen , Anh Duc Vu","doi":"10.1016/j.ymgmr.2025.101286","DOIUrl":"10.1016/j.ymgmr.2025.101286","url":null,"abstract":"<div><div>Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare genetic metabolic disorder involving impaired fatty acid β-oxidation. It is caused by mutations in the Acyl-CoA Dehydrogenase Very Long Chain (ACADVL) gene, which encodes the VLCAD enzyme. The clinical presentation is diverse, ranging from a severe neonatal-onset form to a milder adult-onset form. We describe the first reported case in Vietnam, which is a 20-year-old man who presented with exercise intolerance, myalgia, and recurrent rhabdomyolysis triggered by fasting and exertion. Acylcarnitine profiling suggested a fatty acid oxidation disorder, and whole-exome sequencing identified the diagnosis of VLCAD deficiency with c747G > T (p.Trp249Cys) mutation. It has not previously been reported in the Vietnamese population. This case highlights the important role of neonatal screening and genetic testing in the early diagnosis of metabolic myopathies. In addition, it raises awareness of genetic disorders among healthcare providers and the public in developing countries.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101286"},"PeriodicalIF":1.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898013","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

Full recovery of vision following early and intensive hemodialysis in an 18-year-old woman with methylmalonic acidemia-related optic neuropathy 18岁女性甲基丙二酸血症相关视神经病变患者早期强化血液透析后视力完全恢复

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.ymgmr.2025.101279

Alicia Guertin , Raoul Kanav Khanna , Marine Tardieu , Maud François , Hélène Blasco , Isabelle Benz de Bretagne , Jean-François Benoist , Adrien Bigot , Nathalie Tressel , François Maillot , François Labarthe

Background

Methylmalonic acidemia (MMA) caused by complete or partial deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (mut⁰ or mut- enzymatic subtype, respectively) leads to the accumulation of toxic organic acids, causing severe organ dysfunction and life-threatening complications. Despite appropriate treatment, optic neuropathy has been reported as a vision-threatening complication of MMA, often resulting in debilitating sequelae.

Case report

We present the case of an 18-year-old woman with isolated mut° MMA and with chronic kidney disease stage 3 who presented with a rapid decline in distance and near visual acuity in both eyes. Goldmann visual field perimetry revealed bilateral central relative scotomas with preserved peripheral vision. Visual evoked potentials were unstructured in both eyes, despite normal retinal imaging, indicating optic neuropathy. Metabolic testing revealed elevated levels of methylmalonic acid in both plasma and urine, and increased lactate levels in the plasma and cerebrospinal fluid. Based on the hypothesis of subacute toxicity from methylmalonic acid metabolites, intensive intermittent hemodialysis was initiated, which rapidly decreased the patient's plasma methylmalonic acid level. We also added an oral supplement of coenzyme Q10 and vitamin E. With this treatment, the patient's vision rapidly recovered, and visual function normalized five months later. No progression of optic neuropathy occurred in the eight years follow up after a combined liver/kidney transplant procedure.

Conclusion

Optic neuropathy is a rare long-term complication of isolated MMA, presumably due to the chronic or subacute accumulation of toxic methylmalonic acid metabolites. This case report highlights the importance of early and intensive hemodialysis in achieving favorable visual outcomes by reducing toxic metabolite levels in both blood and central nervous system. In the long-term, liver or combined liver-kidney transplantation should be discussed.

甲基丙二酸血症（MMA）是由线粒体酶甲基丙二酰辅酶a（分别为mut0或mut-酶亚型）的完全或部分缺乏引起的，可导致有毒有机酸的积累，导致严重的器官功能障碍和危及生命的并发症。尽管有适当的治疗，视神经病变已被报道为MMA的视力威胁并发症，通常导致衰弱的后遗症。病例报告：我们报告一例18岁女性孤立性MMA伴慢性肾脏疾病3期，表现为双眼远近视力迅速下降。Goldmann视野检查显示双侧中央相对暗斑，周围视力保留。尽管视网膜成像正常，但两只眼睛的视觉诱发电位未结构化，表明视神经病变。代谢测试显示血浆和尿液中甲基丙二酸水平升高，血浆和脑脊液中乳酸水平升高。基于甲基丙二酸代谢物亚急性毒性的假设，开始强化间歇性血液透析，迅速降低患者血浆甲基丙二酸水平。我们还口服辅酶Q10和维生素e。通过这种治疗，患者的视力迅速恢复，视力功能在5个月后恢复正常。在肝/肾联合移植手术后的8年随访中，视神经病变未发生进展。结论视神经病变是孤立性MMA的一种罕见的长期并发症，可能是由于毒性甲基丙二酸代谢物的慢性或亚急性积累。本病例报告强调了早期和强化血液透析的重要性，通过降低血液和中枢神经系统中有毒代谢物的水平来获得良好的视力结果。从长期来看，应考虑肝移植或肝肾联合移植。

{"title":"Full recovery of vision following early and intensive hemodialysis in an 18-year-old woman with methylmalonic acidemia-related optic neuropathy","authors":"Alicia Guertin , Raoul Kanav Khanna , Marine Tardieu , Maud François , Hélène Blasco , Isabelle Benz de Bretagne , Jean-François Benoist , Adrien Bigot , Nathalie Tressel , François Maillot , François Labarthe","doi":"10.1016/j.ymgmr.2025.101279","DOIUrl":"10.1016/j.ymgmr.2025.101279","url":null,"abstract":"<div><h3>Background</h3><div>Methylmalonic acidemia (MMA) caused by complete or partial deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (mut<sup>0</sup> or mut- enzymatic subtype, respectively) leads to the accumulation of toxic organic acids, causing severe organ dysfunction and life-threatening complications. Despite appropriate treatment, optic neuropathy has been reported as a vision-threatening complication of MMA, often resulting in debilitating sequelae.</div></div><div><h3>Case report</h3><div>We present the case of an 18-year-old woman with isolated mut° MMA and with chronic kidney disease stage 3 who presented with a rapid decline in distance and near visual acuity in both eyes. Goldmann visual field perimetry revealed bilateral central relative scotomas with preserved peripheral vision. Visual evoked potentials were unstructured in both eyes, despite normal retinal imaging, indicating optic neuropathy. Metabolic testing revealed elevated levels of methylmalonic acid in both plasma and urine, and increased lactate levels in the plasma and cerebrospinal fluid. Based on the hypothesis of subacute toxicity from methylmalonic acid metabolites, intensive intermittent hemodialysis was initiated, which rapidly decreased the patient's plasma methylmalonic acid level. We also added an oral supplement of coenzyme Q10 and vitamin E. With this treatment, the patient's vision rapidly recovered, and visual function normalized five months later. No progression of optic neuropathy occurred in the eight years follow up after a combined liver/kidney transplant procedure.</div></div><div><h3>Conclusion</h3><div>Optic neuropathy is a rare long-term complication of isolated MMA, presumably due to the chronic or subacute accumulation of toxic methylmalonic acid metabolites. This case report highlights the importance of early and intensive hemodialysis in achieving favorable visual outcomes by reducing toxic metabolite levels in both blood and central nervous system. In the long-term, liver or combined liver-kidney transplantation should be discussed.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101279"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614653","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

Integrating enzyme assay and molecular genetic testing for early diagnosis of infantile-onset Pompe disease: A case report 结合酶测定和分子基因检测早期诊断婴儿起病庞贝病1例

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.ymgmr.2025.101283

Anuradha Sharma, Minakshi Vashist, Rohit Kaushik, Gulshan Rohilla, Sonia Narwal

Background

Infantile-onset Pompe disease is a severe lysosomal storage disorder caused by biallelic pathogenic variants in GAA, leading to deficient acid α-glucosidase activity.

Case

We report a 6-month-old South Indian male with recurrent respiratory infections, feeding difficulty, generalized hypotonia, and delayed motor milestones. Dried blood spot(DBS) enzyme assay demonstrated markedly reduced acid α-glucosidase activity, and molecular testing identified a homozygous pathogenic variant in GAA (c.2560C > T; p.Arg854*). Parental segregation testing confirmed both parents as heterozygous carriers. Serum creatine phosphokinase was 853 U/L. A cardiac evaluation was recommended but not completed at the time of initial assessment.

Conclusion

This case underscores the diagnostic value of integrating enzyme and molecular testing when infantile-onset Pompe disease is suspected. While newborn screening for Pompe disease exists in some regions, it is not universally implemented, contributing to delays in diagnosis. Early identification allows appropriate counseling and consideration of available management pathways.

Key clinical message

Infantile-onset Pompe disease should be considered in infants presenting with hypotonia, recurrent respiratory infections, feeding difficulties, and delayed motor milestones. Combining dried blood spot enzyme assay with confirmatory molecular testing of the GAA gene enables timely diagnosis, informs counseling, and guides management even in settings where access to enzyme replacement therapy is limited.

背景：早发性庞贝病是由GAA双等位基因致病变异引起的一种严重的溶酶体贮积症，导致酸性α-葡萄糖苷酶活性不足。病例：我们报告一个6个月大的南印度男性复发性呼吸道感染，进食困难，全身性肌张力低下，和延迟运动里程碑。干血斑（DBS）酶检测结果显示酸性α-葡萄糖苷酶活性明显降低，分子检测发现GAA纯合子致病变异（c.2560C >； T; p.Arg854*）。亲本分离试验证实双亲均为杂合携带者。血清肌酸磷酸激酶为853 U/L。建议进行心脏评估，但在最初评估时未完成。结论本病例强调了整合酶和分子检测对婴幼儿起病庞贝病的诊断价值。虽然在一些地区存在新生儿庞贝病筛查，但并未普遍实施，导致诊断延误。早期识别允许适当的咨询和考虑可用的管理途径。主要临床信息：在出现张力低下、反复呼吸道感染、喂养困难和运动发育迟缓的婴儿中，应考虑婴儿期起病的庞贝病。将干血斑酶测定与GAA基因的确证性分子检测相结合，即使在酶替代治疗有限的情况下，也能及时诊断，提供咨询，指导管理。

{"title":"Integrating enzyme assay and molecular genetic testing for early diagnosis of infantile-onset Pompe disease: A case report","authors":"Anuradha Sharma, Minakshi Vashist, Rohit Kaushik, Gulshan Rohilla, Sonia Narwal","doi":"10.1016/j.ymgmr.2025.101283","DOIUrl":"10.1016/j.ymgmr.2025.101283","url":null,"abstract":"<div><h3>Background</h3><div>Infantile-onset Pompe disease is a severe lysosomal storage disorder caused by biallelic pathogenic variants in <strong><em>GAA</em></strong>, leading to deficient acid α-glucosidase activity.</div></div><div><h3>Case</h3><div>We report a 6-month-old South Indian male with recurrent respiratory infections, feeding difficulty, generalized hypotonia, and delayed motor milestones. <strong>Dried blood spot</strong>(DBS) enzyme assay demonstrated markedly reduced acid α-glucosidase activity, and molecular testing identified a homozygous pathogenic variant in <strong><em>GAA</em></strong> (c.2560C > T; p.Arg854*). Parental segregation testing confirmed both parents as heterozygous carriers. Serum creatine phosphokinase was 853 U/L. A cardiac evaluation was recommended but not completed at the time of initial assessment.</div></div><div><h3>Conclusion</h3><div>This case underscores the diagnostic value of integrating enzyme and molecular testing when infantile-onset Pompe disease is suspected. While newborn screening for Pompe disease exists in some regions, it is not universally implemented, contributing to delays in diagnosis. Early identification allows appropriate counseling and consideration of available management pathways.</div></div><div><h3>Key clinical message</h3><div>Infantile-onset Pompe disease should be considered in infants presenting with hypotonia, recurrent respiratory infections, feeding difficulties, and delayed motor milestones. Combining dried blood spot enzyme assay with confirmatory molecular testing of the <strong><em>GAA</em></strong> gene enables timely diagnosis, informs counseling, and guides management even in settings where access to enzyme replacement therapy is limited.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101283"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733134","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

Clinical and molecular spectrum of mucopolysaccharidosis IVA in Iraqi children: Allele-specific genotype–phenotype trends and novel GALNS variants 伊拉克儿童粘多糖病IVA的临床和分子谱：等位基因特异性基因型-表型趋势和新的GALNS变异

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.ymgmr.2025.101281

Saja Baheer Abdul Wahhab , Rabab Farhan Thejeal

Background

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare lysosomal storage disorder that causes early-onset skeletal dysplasia and progressive multisystem involvement. Although international cohorts have been described, population-specific data from the Middle East remain limited.

Objective

This study aimed to characterize the clinical spectrum, functional status, and GALNS variant profile in Iraqi children with MPS IVA, and to assess diagnostic timing in comparison with international experience.

Methods

We retrospectively analyzed 33 children from 26 unrelated families with confirmed MPS IVA, recruited at the Children's Welfare Teaching Hospital in Baghdad between 2016 and 2022. Enzyme activity was measured on dried blood spots by LC-MS/MS, and GALNS variants were identified using next-generation sequencing with Sanger confirmation. Clinical evaluation included anthropometry, echocardiography, ophthalmologic and audiologic assessments, skeletal surveys, and functional endurance testing (6-min walk test and 3-min stair-climb).

Results

Fifteen distinct GALNS variants were identified, including five novel variants (three missense, two frameshift). The most common allele was c.949G > A (p.Gly317Arg), consistently associated with severe phenotypes and absent enzyme activity. Universal skeletal dysplasia was observed, with frequent corneal clouding, cardiac valve disease, and reduced functional endurance. Symptoms typically appeared in early childhood, but definitive diagnosis was often delayed until later childhood or adolescence. Allele-specific genotype–phenotype trends were observed, though no statistically significant correlations could be established due to limited cohort size.

Conclusion

This first Iraqi cohort expands the GALNS variant spectrum and highlights persistent diagnostic delays despite early clinical manifestations. Early molecular confirmation, establishment of national registries, and multidisciplinary surveillance are essential to reduce long-term morbidity.

背景：粘多糖病型IVA （MPS IVA； Morquio A综合征）是一种罕见的溶酶体沉积疾病，可导致早发性骨骼发育不良和进行性多系统受累。虽然已经描述了国际队列，但来自中东的特定人群数据仍然有限。目的本研究旨在描述伊拉克MPS IVA患儿的临床谱、功能状态和GALNS变异谱，并与国际经验进行比较，评估诊断时机。方法回顾性分析2016年至2022年在巴格达儿童福利教学医院招募的26个非亲属家庭确诊MPS IVA的33名儿童。用LC-MS/MS测定干血斑上的酶活性，并采用Sanger确认的下一代测序方法鉴定GALNS变异。临床评估包括人体测量、超声心动图、眼科和听力学评估、骨骼调查和功能耐力测试（6分钟步行测试和3分钟爬楼梯）。结果鉴定出15种不同的GALNS变异，包括5种新变异（3种错义，2种移码）。最常见的等位基因是c.949G > A (p.Gly317Arg)，与严重表型和缺乏酶活性一致相关。观察到普遍的骨骼发育不良，角膜混浊，心脏瓣膜疾病和功能耐力降低。症状通常出现在儿童早期，但明确的诊断往往延迟到儿童后期或青春期。观察到等位基因特异性基因型-表型趋势，但由于队列规模有限，无法建立统计学上显著的相关性。结论：第一个伊拉克队列扩展了GALNS变异谱，突出了尽管早期临床表现，但持续的诊断延迟。早期分子确认、建立国家登记和多学科监测对于降低长期发病率至关重要。

{"title":"Clinical and molecular spectrum of mucopolysaccharidosis IVA in Iraqi children: Allele-specific genotype–phenotype trends and novel GALNS variants","authors":"Saja Baheer Abdul Wahhab , Rabab Farhan Thejeal","doi":"10.1016/j.ymgmr.2025.101281","DOIUrl":"10.1016/j.ymgmr.2025.101281","url":null,"abstract":"<div><h3>Background</h3><div>Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare lysosomal storage disorder that causes early-onset skeletal dysplasia and progressive multisystem involvement. Although international cohorts have been described, population-specific data from the Middle East remain limited.</div></div><div><h3>Objective</h3><div>This study aimed to characterize the clinical spectrum, functional status, and <em>GALNS</em> variant profile in Iraqi children with MPS IVA, and to assess diagnostic timing in comparison with international experience.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 33 children from 26 unrelated families with confirmed MPS IVA, recruited at the Children's Welfare Teaching Hospital in Baghdad between 2016 and 2022. Enzyme activity was measured on dried blood spots by LC-MS/MS, and <em>GALNS</em> variants were identified using next-generation sequencing with Sanger confirmation. Clinical evaluation included anthropometry, echocardiography, ophthalmologic and audiologic assessments, skeletal surveys, and functional endurance testing (6-min walk test and 3-min stair-climb).</div></div><div><h3>Results</h3><div>Fifteen distinct <em>GALNS</em> variants were identified, including five novel variants (three missense, two frameshift). The most common allele was c.949G > A (p.Gly317Arg), consistently associated with severe phenotypes and absent enzyme activity. Universal skeletal dysplasia was observed, with frequent corneal clouding, cardiac valve disease, and reduced functional endurance. Symptoms typically appeared in early childhood, but definitive diagnosis was often delayed until later childhood or adolescence. Allele-specific genotype–phenotype trends were observed, though no statistically significant correlations could be established due to limited cohort size.</div></div><div><h3>Conclusion</h3><div>This first Iraqi cohort expands the <em>GALNS</em> variant spectrum and highlights persistent diagnostic delays despite early clinical manifestations. Early molecular confirmation, establishment of national registries, and multidisciplinary surveillance are essential to reduce long-term morbidity.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101281"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614652","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

A novel SLC17A5 variant in infantile sialic acid storage disease with hyporegenerative anemia: Neuroimaging insights and literature review 一种新的SLC17A5变异在婴儿唾液酸储存病伴低再生性贫血：神经影像学见解和文献综述

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.ymgmr.2025.101284

Francesca Cappozzo , Mariasavina Severino , Elena Gennaro , Francesca Faravelli , Marina Martinez Popple , Maria Cristina Schiaffino , Annalisa Madeo , Alessandro La Rosa

Infantile sialic acid storage disorder (ISSD) represents the most severe form of free sialic acid storage disease (FSASD), a rare lysosomal storage disorder caused by mutations in SLC17A5, which encodes the lysosomal sialic acid transporter sialin. These mutations lead to the accumulation of free sialic acid within lysosomes, resulting in multisystemic involvement. Through a case report and literature review, we explored the phenotypic spectrum of FSASD, with a particular focus on neurological manifestations and characteristic neuroimaging findings of ISSD. Our patient exhibited severe hypotonia shortly after birth, dysmorphic features, and hyporegenerative anemia, a clinical presentation that has not previously described in ISSD. Brain MRI revealed hypomyelination, periventricular white matter T1-hyperintensity and T2-hypointensity, callosal thinning, and optic atrophy, providing critical diagnostic clues. MR spectroscopy showed an elevated NAA-like peak, further supporting the suspicion of ISSD. Laboratory tests demonstrated increased chitotriosidase activity and elevated urinary excretion of free sialic acid. Next-generation sequencing identified compound heterozygosity for a known pathogenic variant and a previously unreported SLC17A5 variant (c.709G>A), affecting a highly conserved transmembrane domain residue and predicted to be pathogenic.

Our findings underscore the role of neuroimaging in the early diagnosis of ISSD and suggest a potential link between sialic acid metabolism and erythropoiesis, suggesting further investigation. Despite the lack of targeted therapies, recognizing FSASD remains essential for patient management and genetic counselling, ensuring appropriate clinical care and family support.

婴儿唾液酸储存障碍（ISSD）是游离唾液酸储存疾病（FSASD）的最严重形式，这是一种罕见的溶酶体储存疾病，由编码溶酶体唾液酸转运蛋白sialin的SLC17A5突变引起。这些突变导致游离唾液酸在溶酶体内的积累，导致多系统参与。通过病例报告和文献回顾，我们探讨了fssd的表型谱，特别关注ISSD的神经学表现和特征性神经影像学表现。我们的患者在出生后不久就表现出严重的张力低下，畸形特征和再生障碍性贫血，这些临床表现在ISSD中以前没有描述过。脑MRI显示髓鞘硬化、脑室周围白质t1高、t2低、胼胝体变薄、视神经萎缩，为诊断提供了重要线索。MR谱显示na样峰升高，进一步支持ISSD的怀疑。实验室测试显示壳三酸苷酶活性增加，尿中游离唾液酸排泄量增加。新一代测序鉴定出一种已知致病变异和一种以前未报道的SLC17A5变异（c.709G> a）的复合杂合性，影响一个高度保守的跨膜结构域残基，预计具有致病性。我们的研究结果强调了神经影像学在ISSD早期诊断中的作用，并提示唾液酸代谢与红细胞生成之间的潜在联系，建议进一步研究。尽管缺乏靶向治疗，但认识到fssd对于患者管理和遗传咨询，确保适当的临床护理和家庭支持仍然至关重要。

{"title":"A novel SLC17A5 variant in infantile sialic acid storage disease with hyporegenerative anemia: Neuroimaging insights and literature review","authors":"Francesca Cappozzo , Mariasavina Severino , Elena Gennaro , Francesca Faravelli , Marina Martinez Popple , Maria Cristina Schiaffino , Annalisa Madeo , Alessandro La Rosa","doi":"10.1016/j.ymgmr.2025.101284","DOIUrl":"10.1016/j.ymgmr.2025.101284","url":null,"abstract":"<div><div>Infantile sialic acid storage disorder (ISSD) represents the most severe form of free sialic acid storage disease (FSASD), a rare lysosomal storage disorder caused by mutations in <em>SLC17A5</em>, which encodes the lysosomal sialic acid transporter sialin. These mutations lead to the accumulation of free sialic acid within lysosomes, resulting in multisystemic involvement. Through a case report and literature review, we explored the phenotypic spectrum of FSASD, with a particular focus on neurological manifestations and characteristic neuroimaging findings of ISSD. Our patient exhibited severe hypotonia shortly after birth, dysmorphic features, and hyporegenerative anemia, a clinical presentation that has not previously described in ISSD. Brain MRI revealed hypomyelination, periventricular white matter T1-hyperintensity and T2-hypointensity, callosal thinning, and optic atrophy, providing critical diagnostic clues. MR spectroscopy showed an elevated NAA-like peak, further supporting the suspicion of ISSD. Laboratory tests demonstrated increased chitotriosidase activity and elevated urinary excretion of free sialic acid. Next-generation sequencing identified compound heterozygosity for a known pathogenic variant and a previously unreported <em>SLC17A5</em> variant (c.709G>A), affecting a highly conserved transmembrane domain residue and predicted to be pathogenic.</div><div>Our findings underscore the role of neuroimaging in the early diagnosis of ISSD and suggest a potential link between sialic acid metabolism and erythropoiesis, suggesting further investigation. Despite the lack of targeted therapies, recognizing FSASD remains essential for patient management and genetic counselling, ensuring appropriate clinical care and family support.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101284"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733129","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

Mucopolysaccharidoses: A biochemical study under limited resources 粘多糖：有限资源下的生化研究

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports

Pub Date : 2025-11-20 DOI: 10.1016/j.ymgmr.2025.101280

Fadoua Bouzid , Houda El Fissi , Khadija Karim , Mohamed Said Sebbar , Bouchaib Jabir , Nouzha Chuis , Fouad Msanda , Najat Alif

The mucopolysaccharidoses are a heterogeneous group of lysosomal storage disorders caused by deficiencies of enzymes involved in degradation of glycosaminoglycans. This study aimed to share our experience with biochemical investigations of these disorders under resource-limited conditions. Harmine extract was obtained from Peganum harmala seeds, and chromatography plates were homemade. Biochemical analysis involved urinary tests, including the Berry Spot test, the quantification of the glycosaminoglycans, as well as their characterization, and the analysis of deficient enzymes. The reference range values of glycosaminoglycans and activities of seven lysosomal enzymes, six of which are associated with these disorders were initially determined in samples of healthy subjects. The assay for β-galactosidase was described. These biochemical markers were then, evaluated in 29 patients, including 23 who were suspected of having different types of mucopolysaccharidoses and six who were diagnosed with the type I and undergoing enzymotherapy. The reference values of glycosaminoglycans and enzymes activities align with those reported in the literature. The reference value of β-galactosidase ranges from 83 to 311 nmol/17 h/mg. All the studied patients have shown the same positive pattern of Berry Spot Test in contrast of the healthy subjects. The level of GAGs was elevated by 1.1 to more than six fold but is decreased by more than six fold in patients with mucopolysaccharidosis type 1 undergoing enzymotherapy. The patients were categorized as follows: Hurler syndrome 34 %, Hunter syndrome 7 %, Sanfilippo syndrome 17 %, and Morquio syndrome 41 %. In patients for whom molecular defects were characterized, the mutations were correlated with the biochemical markers.

粘多糖病是一种由参与糖胺聚糖降解的酶缺乏引起的异质溶酶体储存障碍。本研究旨在分享我们在资源有限条件下对这些疾病进行生化调查的经验。从苦参种子中提取苦参碱，自制层析板。生化分析包括尿液测试，包括浆果斑测试，糖胺聚糖的定量分析及其特征，以及缺陷酶的分析。糖胺聚糖的参考值和7种溶酶体酶的活性，其中6种与这些疾病有关，最初在健康受试者的样本中确定。介绍了β-半乳糖苷酶的测定方法。然后，对29名患者进行了这些生化标记物的评估，其中包括23名怀疑患有不同类型粘多糖病的患者和6名诊断为I型并接受酶治疗的患者。糖胺聚糖和酶活性的参考值与文献报道一致。β-半乳糖苷酶的参考值为83 ~ 311 nmol/17 h/mg。所有研究对象均表现出与正常人相同的浆果斑试验阳性模式。GAGs水平升高1.1倍至6倍以上，但在接受酶治疗的1型粘多糖病患者中，GAGs水平下降6倍以上。患者分为：Hurler综合征34%，Hunter综合征7%，Sanfilippo综合征17%，Morquio综合征41%。在具有分子缺陷特征的患者中，突变与生化标志物相关。

{"title":"Mucopolysaccharidoses: A biochemical study under limited resources","authors":"Fadoua Bouzid , Houda El Fissi , Khadija Karim , Mohamed Said Sebbar , Bouchaib Jabir , Nouzha Chuis , Fouad Msanda , Najat Alif","doi":"10.1016/j.ymgmr.2025.101280","DOIUrl":"10.1016/j.ymgmr.2025.101280","url":null,"abstract":"<div><div>The mucopolysaccharidoses are a heterogeneous group of lysosomal storage disorders caused by deficiencies of enzymes involved in degradation of glycosaminoglycans. This study aimed to share our experience with biochemical investigations of these disorders under resource-limited conditions. Harmine extract was obtained from <em>Peganum harmala</em> seeds, and chromatography plates were homemade. Biochemical analysis involved urinary tests, including the Berry Spot test, the quantification of the glycosaminoglycans, as well as their characterization, and the analysis of deficient enzymes. The reference range values of glycosaminoglycans and activities of seven lysosomal enzymes, six of which are associated with these disorders were initially determined in samples of healthy subjects. The assay for β-galactosidase was described. These biochemical markers were then, evaluated in 29 patients, including 23 who were suspected of having different types of mucopolysaccharidoses and six who were diagnosed with the type I and undergoing enzymotherapy. The reference values of glycosaminoglycans and enzymes activities align with those reported in the literature. The reference value of β-galactosidase ranges from 83 to 311 nmol/17 h/mg. All the studied patients have shown the same positive pattern of Berry Spot Test in contrast of the healthy subjects. The level of GAGs was elevated by 1.1 to more than six fold but is decreased by more than six fold in patients with mucopolysaccharidosis type 1 undergoing enzymotherapy. The patients were categorized as follows: Hurler syndrome 34 %, Hunter syndrome 7 %, Sanfilippo syndrome 17 %, and Morquio syndrome 41 %. In patients for whom molecular defects were characterized, the mutations were correlated with the biochemical markers.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101280"},"PeriodicalIF":1.9,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568413","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