Molecular Genetics and Metabolism Reports最新文献

{"title":"A novel GATA3 frameshift mutation causes hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome","authors":"Bo Huang ,&nbsp;Shiwei Li ,&nbsp;Yun Chai ,&nbsp;Yu Fan,&nbsp;Xin Li,&nbsp;Yue Liu,&nbsp;Yunhong Fu,&nbsp;Xixi Song,&nbsp;Jingqiu Cui","doi":"10.1016/j.ymgmr.2024.101063","DOIUrl":"10.1016/j.ymgmr.2024.101063","url":null,"abstract":"<div><h3>Background</h3><p>Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome (Barakat syndrome) is a rare autosomal dominant disorder caused by mutations in the gene encoding <em>GATA3</em> on chromosome 10p14.</p></div><div><h3>Method</h3><p>Informed consent was obtained from a 38-year-old female patient. 5 mL of venous blood was collected and sent for whole-exome sequencing. <em>GATA3</em> constructs of both wild-type and mutant were transfected into HEK-293 T cells. Three-dimensional modeling, luciferase-reporter gene test, western blotting and cellular immunofluorescence were used to evaluate the effect of the mutation.</p></div><div><h3>Results</h3><p>A novel frameshift mutation c. 677dup(p.Pro227AlafsTer77), named P227Afs, was found in <em>GATA3</em>. Three-dimensional modeling revealed that the mutation caused the loss of the dual zinc finger structures 1 and 2 (ZNF1 and ZNF2) of the synthesized protein. Expression of wild-type GATA3 produced a six-fold increase in luciferase activity when compared with pcDNA3.1 vector only (<em>P</em> &lt; 0.001), whereas the P227Afs mutant showed no increase. The mutation significantly reduced the transcriptional activity of <em>GATA3</em>. Immunofluorescence and western blotting analyses demonstrated that the mutation changed the nuclear location of GATA3 and caused difficulty in nuclearization.</p></div><div><h3>Conclusion</h3><p>A novel heterozygous frameshift mutation in <em>GATA3</em> was identified and showed to result in difficult nuclearization, and a dominant-negative effect on the wild-type.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000168/pdfft?md5=521b2443814e15ed421259ec40ed5e67&pid=1-s2.0-S2214426924000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact on physical, social, and family functioning of patients with metachromatic leukodystrophy and their family members in Japan: A qualitative study","authors":"Yuta Koto ,&nbsp;Wakana Yamashita ,&nbsp;Norio Sakai","doi":"10.1016/j.ymgmr.2024.101059","DOIUrl":"10.1016/j.ymgmr.2024.101059","url":null,"abstract":"<div><p>Metachromatic leukodystrophy is a rare autosomal recessive disease. There are three forms of this disease, all of which result in cognitive and motor dysfunctions. Although enzyme replacement and gene therapies have been developed, they are not expected to be effective in patients with advanced diseases. Therefore, it is important to focus on treatment effects and patients' quality of life; however, qualitative findings on the experiences of patients and their families have not been adequately reported. Interviews were conducted with the family members of patients with metachromatic leukodystrophy in Japan. Verbatim transcripts were analyzed using a qualitative content analysis approach. We interviewed the mothers of five patients. Verbatim interview transcripts were classified into 81 codes. The codes were then aggregated into 15 categories and 3 themes: challenges of life for the patients, challenges in the healthcare system, and challenges of family function. Disease progression greatly affects patients' lives. Moreover, social systems supporting patients and their families are inadequate, especially as the disease progresses. Family members face life restrictions and role changes because of the patient's diagnosis. Patients with metachromatic leukodystrophy and their families require comprehensive support.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000120/pdfft?md5=373773e29f0ea596820ec58e86c88388&pid=1-s2.0-S2214426924000120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stealthy progression of type 2 diabetes mellitus due to impaired ketone production in an adult patient with multiple acyl-CoA dehydrogenase deficiency","authors":"Nodoka Ikeda ,&nbsp;Yoichi Wada ,&nbsp;Tomohito Izumi ,&nbsp;Yuichiro Munakata ,&nbsp;Hideki Katagiri ,&nbsp;Shigeo Kure","doi":"10.1016/j.ymgmr.2024.101061","DOIUrl":"10.1016/j.ymgmr.2024.101061","url":null,"abstract":"<div><h3>Background</h3><p>Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disorder caused by biallelic pathogenic variants in genes related to the flavoprotein complex. Dysfunction of the complex leads to impaired fatty acid oxidation and ketone body production which can cause hypoketotic hypoglycemia with prolonged fasting. Patients with fatty acid oxidation disorders (FAODs) such as MADD are treated primarily with a dietary regimen consisting of high-carbohydrate foods and avoidance of prolonged fasting. However, information on the long-term sequelae associated with this diet have not been accumulated. In general, high-carbohydrate diets can induce diseases such as type 2 diabetes mellitus (T2DM), although few patients with both MADD and T2DM have been reported.</p></div><div><h3>Case</h3><p>We present the case of a 32-year-old man with MADD who was on a high-carbohydrate diet for &gt;30 years and exhibited symptoms resembling diabetic ketoacidosis. He presented with polydipsia, polyuria, and weight loss with a decrease in body mass index from 31 to 25 kg/m² over 2 months. Laboratory tests revealed a HbA1c level of 13.9%; however, the patient did not show metabolic acidosis but only mild ketosis.</p></div><div><h3>Discussion/conclusion</h3><p>This report emphasizes the potential association between long-term adherence to high-carbohydrate dietary therapy and T2DM development. Moreover, this case underscores the difficulty of detecting diabetic ketosis in patients with FAODs such as MADD due to their inability to produce ketone bodies. These findings warrant further research of the long-term complications associated with this diet as well as warning of the potential progression of diabetes in patients with FAODs such as MADD.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000144/pdfft?md5=e35ff4322872f496f37fad8a8daf8d87&pid=1-s2.0-S2214426924000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and biochemical phenotypes, genotypes, and long-term outcomes of individuals with galactosemia type I from a single metabolic genetics center in Alberta","authors":"Nihal Almenabawy ,&nbsp;Shalini Bahl ,&nbsp;Alyssa-Lyn Ostlund ,&nbsp;Shailly Ghai-Jain ,&nbsp;Iveta Sosova ,&nbsp;Alicia Chan ,&nbsp;Saadet Mercimek-Andrews","doi":"10.1016/j.ymgmr.2024.101055","DOIUrl":"10.1016/j.ymgmr.2024.101055","url":null,"abstract":"<div><h3>Background</h3><p>Galactosemia type I is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase deficiency, encoded by <em>GALT</em>. To investigate the phenotypes, genotypes and long-term outcomes of galactosemia, we performed a retrospective cohort study in our center.</p></div><div><h3>Methods</h3><p>All individuals with galactosemia type I were included. We divided individuals into two groups to compare the outcomes of those treated symptomatically (SymX) and asymptomatically (AsymX). We reviewed electronic patient charts for clinical features, biochemical investigations, molecular genetic investigations, treatments, and outcomes.</p></div><div><h3>Results</h3><p>There were 25 individuals including classic (<em>n</em> = 17), clinical variant (<em>n</em> = 4), and biochemical variant (Duarte) galactosemia (<em>n</em> = 4). Twelve individuals were diagnosed symptomatically (SymX), and 9 individuals were diagnosed asymptomatically (AsymX). We did not include individuals with biochemical variant (Duarte) galactosemia into any of these groups. At the time of the diagnosis, conjugated hyperbilirubinemia was present in 83.3% of SymX group, whereas only 22% of AsymX group. SymX group had hepatomegaly (25%), failure to thrive (33.3%), cataract (16.7%) and sepsis (25%), whereas none of the individuals in the AsymX group had these clinical features. Fourteen variants in <em>GALT</em> were identified including pathogenic/likely pathogenic (<em>n</em> = 12), and likely benign/benign (<em>n</em> = 2) variants. The vast majority of individuals with classic and clinical variant galactosemia were treated with a galactose-lactose-free diet for life (<em>n</em> = 20/21). Intellectual disability was present in 54.5% of the SymX group, and in 37.5% of the AsymX group as a long-term outcome. Tremors were present 50% of the SymX group, and in 22% of the AsymX group as a long-term outcome. Although, intellectual disability and tremors seem to be less common in the AsymX group, there was no statistically significant difference between both groups. Primary ovarian insufficiency was present 50% of the SymX group, whereas in 20% of the AsymX group in post-pubertal females. We report a novel hypomorphic <em>GALT</em> variant (p.Ala303Ser) in one individual with clinical variant galactosemia. We also report an individual with clinical variant galactosemia with normal urine galactitol levels on a normal diet.</p></div><div><h3>Conclusion</h3><p>It seems that newborn screening and early administration of a galactose-lactose-free diet decreases the long-term galactosemia-associated complications but does not prevent them completely. It may be that not all individuals with clinical variant galactosemia may need a galactose-lactose-free diet. It is timely to find new therapeutic strategies that can reduce the frequency of late-onset complications in galactosemia.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000089/pdfft?md5=490d5de4832a421ffce1185744d9c466&pid=1-s2.0-S2214426924000089-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-linked intellectual developmental disorder with onset of neonatal heart failure: A case report and literature review","authors":"Hongmin Xi,&nbsp;Lili Ma,&nbsp;Xiangyun Yin,&nbsp;Ping Yang,&nbsp;Xianghong Li,&nbsp;Liangliang Li","doi":"10.1016/j.ymgmr.2024.101054","DOIUrl":"10.1016/j.ymgmr.2024.101054","url":null,"abstract":"<div><p>X-linked intellectual developmental disorder is a rare X-linked genetic disease, manifested as heart disease, intellectual impairment, and developmental disorders.</p><p>We report a male infant who presented with dyspnea after birth. Physical examination on admission revealed poor responsiveness, deep eye sockets, a small mandible, abnormalities of the outer ears, and reduced limb muscle tone. The child was moaning with shortness of breath and a positive three-concave sign without pulmonary rales. The heart sounds were weak with a grade 2/6 diastolic heart murmur. Echocardiography showed an enlarged heart with increased trabeculae in the left ventricular muscle wall. X-linked mental retardation syndrome type 34(MRXS34, OMIM# <span>300967</span><svg><path></path></svg>) was diagnosed after exome sequencing showed a c.1131G &gt; A hemizygous variant in the <em>NONO</em> gene. After timely therapy including respiratory support, cardiac glycosides, and diuresis, the child's condition improved and he was discharged at one month of age.</p><p>A literature review showed that, to date, 22 live births with X-linked mental retardation have been reported^. The <em>NONO</em>-related phenotype can be summarized as a neurological and cardiac developmental disorder, which may be accompanied by multisystem malformations. The present case enriches the knowledge of X-linked intellectual developmental syndromes.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000077/pdfft?md5=8eaaf531f78c70102de1ac80fb709cc8&pid=1-s2.0-S2214426924000077-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139556926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural history of three late-diagnosed classic Galactosemia patients","authors":"Dulce Quelhas ,&nbsp;Sandra D.K. Kingma ,&nbsp;An I. Jonckheere ,&nbsp;Claudia S. Smeets-Peels ,&nbsp;Daniel Costa Gomes ,&nbsp;José Duro ,&nbsp;Anabela Oliveira ,&nbsp;Gert Matthijs ,&nbsp;Laura K.M. Steinbusch ,&nbsp;Jaak Jaeken ,&nbsp;Isabel Rivera ,&nbsp;Estela Rubio-Gozalbo","doi":"10.1016/j.ymgmr.2024.101057","DOIUrl":"10.1016/j.ymgmr.2024.101057","url":null,"abstract":"<div><p>The authors report the natural history of three patients with late-diagnosed Classic Galactosemia (CG) (at 16, 19 and 28 years). This was due to a combination of factors: absence of neonatal screening, absence of some typical acute neonatal symptoms, and negative galactosemia screening. This report underlines the value of neonatal screening and the importance of further diagnostic testing in case of late-onset manifestations.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000107/pdfft?md5=7180180ad300a8a3741f10952aee6043&pid=1-s2.0-S2214426924000107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel GK Ala469Val variant resulting in glycerol kinase deficiency with concurrent hepatoblastoma: A case report","authors":"Domenic Filingeri ,&nbsp;Sarah Mackey ,&nbsp;Haley Soller ,&nbsp;Alissa Guarneri-Tragone ,&nbsp;James Cooper ,&nbsp;Oscar Escobar ,&nbsp;Jirair K. Bedoyan","doi":"10.1016/j.ymgmr.2024.101058","DOIUrl":"10.1016/j.ymgmr.2024.101058","url":null,"abstract":"<div><p>Glycerol kinase deficiency (GKD) is a rare X-linked condition where glycerol cannot be phosphorylated to glycerol-3-phosphate, a key component of gluconeogenesis. Clinical presentation varies widely. We present a novel variant of the responsible <em>GK</em> in a patient with concurrent hepatoblastoma, whose course was complicated by hypoglycemia. Hepatoblastoma has not previously been described with GKD, highlighting the need for further research into GKD and its potential role in the pathogenesis of some forms of hepatoblastoma.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000119/pdfft?md5=a68466f4ce979722e2db3131c3e5d4df&pid=1-s2.0-S2214426924000119-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance and application of WES in fetal genetic diagnostics: Identification of novel ASPM mutation in a fetus with microcephaly","authors":"Renata Szalai ,&nbsp;Agnes Till ,&nbsp;Attila Gyenesei ,&nbsp;Judit Bene ,&nbsp;Kinga Hadzsiev","doi":"10.1016/j.ymgmr.2024.101056","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101056","url":null,"abstract":"<div><h3>Background</h3><p>Prenatal whole exome sequencing (WES) approaches can provide genetic diagnosis with rapid turnaround time and high diagnostic rate when conventional tests are negative. Here we report a family with multiple pregnancy loss and with repeated occurrence of fetal microcephaly.</p></div><div><h3>Methods and results</h3><p>Because of positive family history and recurrent structural abnormality during the pregnancies that may lead postnatal neurodevelopmental consequences, WES analysis was indicated. Umbilical cord blood sampling was carried out and WES was performed using Twist Human Core Exome Kit and Illumina sequencing technology. The presence of pathogenic variants was confirmed by Sanger sequencing. WES analysis revealed a known pathogenic c.8506_8507delCA (p.Gln2836Glufs*35, rs587783280) and a novel pathogenic c.3134_3135delTC (p.Leu1045Glnfs*17) <em>ASPM</em> mutations in the fetus in compound heterozygous state. The c.3134_3135delTC has never been reported in the literature.</p></div><div><h3>Conclusions</h3><p>Our findings serve additional evidence that WES can be an efficient and relevant tool to diagnose certain genetic disorders with appropriate indication and to assess the recurrence risk of a disease. With the application of WES in combination with pre-implantation genetic tests, we can avoid the transmission of pathogenic mutations and we can achieve a decreased abortion rate in obstetric care.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000090/pdfft?md5=a734c9c72cbe5e93f65df382fd7305b0&pid=1-s2.0-S2214426924000090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139487474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long term follow-up in GAMT deficiency – Correlation of therapy regimen, biochemical and in vivo brain proton MR spectroscopy data","authors":"Lara M. Marten ,&nbsp;Ralph Krätzner ,&nbsp;Gajja S. Salomons ,&nbsp;Matilde Fernandez Ojeda ,&nbsp;Peter Dechent ,&nbsp;Jutta Gärtner ,&nbsp;Peter Huppke ,&nbsp;Steffi Dreha-Kulaczewski","doi":"10.1016/j.ymgmr.2024.101053","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101053","url":null,"abstract":"<div><p>GAMT deficiency is a rare autosomal recessive disease within the group of cerebral creatine deficiency syndromes. Cerebral creatine depletion and accumulation of guanidinoacetate (GAA) lead to clinical presentation with intellectual disability, seizures, speech disturbances and movement disorders. Treatment consists of daily creatine supplementation to increase cerebral creatine, reduction of arginine intake and supplementation of ornithine for reduction of toxic GAA levels. This study represents the first long-term follow-up over a period of 14 years, with detailed clinical data, biochemical and multimodal neuroimaging findings. Developmental milestones, brain MRI, quantitative single voxel ¹H magnetic resonance spectroscopy (MRS) and biochemical analyses were assessed. The results reveal insights into the dose dependent effects of creatine/ornithine supplementation and expand the phenotypic spectrum of GAMT deficiency. Of note, the creatine concentrations, which were regularly monitored over a long follow-up period, increased significantly over time, but did not reach age matched control ranges. Our patient is the second reported to show normal neurocognitive outcome after an initial delay, stressing the importance of early diagnosis and treatment initiation.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000065/pdfft?md5=48a68ba797aaae70869c72009379704b&pid=1-s2.0-S2214426924000065-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139494104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic odyssey for patients with acid sphingomyelinase deficiency (ASMD): Exploring the potential indicators of diagnosis using quantitative and qualitative data","authors":"Andrew Doerr ,&nbsp;Maliha Farooq ,&nbsp;Chad Faulkner ,&nbsp;Rebecca Gould ,&nbsp;Krista Perry ,&nbsp;Ruth Pulikottil-Jacob ,&nbsp;Pamela Rajasekhar","doi":"10.1016/j.ymgmr.2024.101052","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101052","url":null,"abstract":"<div><p>Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and potentially fatal lysosomal storage disease. This two-part international study aimed to understand physician, patient, and caregivers' experiences during the ASMD diagnostic journey. Qualitative interviews were conducted with patients with ASMD type B or A/B, caregivers (for patients &lt;18 years), and physicians (January 2018–May 2019). A quantitative patient chart review was then performed by physicians (1–3 charts per physician) (April to May 2020). Overall, 12 physicians and 27 patients (self-reported, <em>n</em> = 11; caregiver-reported, <em>n</em> = 16) completed qualitative interviews. Symptoms first presented at approximately 2 years, with physician visits 2 months–1 year later. On average, diagnosis took 3 years and average age at diagnosis was 5 years. During childhood, all patients reported abdominal enlargement and 67% had respiratory issues. Adult patients frequently reported fatigue (64%) and heart problems (36%). In the quantitative study, 86 physicians reviewed 193 ASMD patient charts. At initial presentation, most patients reported abdominal enlargement (pediatric, 55%; adolescents/adults, 39%). Time to diagnosis ranged 0–10 years for patients with ASMD type A/B or type B, and most patients (85%) received an incorrect initial diagnosis. Diagnosis of ASMD can be challenging, and is often delayed due to disease heterogeneity and misdiagnoses.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000053/pdfft?md5=e8f3f22913765137a4276e31ff2d3117&pid=1-s2.0-S2214426924000053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139480183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}