Molecular Genetics and Metabolism Reports最新文献

{"title":"First combined analysis of SMN1, SMN2, and NAIP copy numbers in Moroccan SMA patients and their correlation with disease severity","authors":"Samira Nmer ,&nbsp;Said Trhanint ,&nbsp;Hanane Sayel ,&nbsp;Sana Chaouki ,&nbsp;Laila Bouguenouch ,&nbsp;Karim Ouldim","doi":"10.1016/j.ymgmr.2026.101299","DOIUrl":"10.1016/j.ymgmr.2026.101299","url":null,"abstract":"<div><h3>Background</h3><div>Spinal muscular atrophy (SMA) is a neuromuscular disorder caused in 95% of cases by homozygous <em>SMN1</em> exon 7 deletion, with severity primarily determined by the modifier genes <em>SMN2</em> and <em>NAIP</em> copy numbers.</div></div><div><h3>Objective</h3><div>This study, the first in the Moroccan population, simultaneously analyzed <em>SMN1</em>, <em>SMN2</em>, and <em>NAIP</em> copy numbers to investigate their relationship with SMA severity and their utility in predicting patients' phenotype.</div></div><div><h3>Methods</h3><div>RFLP-PCR was used to screen 214 patients for <em>SMN1</em> exon 7 homozygous deletion. In patients with confirmed SMA, copy number variations (CNVs) of <em>SMN1</em>, <em>SMN2</em>, and <em>NAIP</em> were analyzed by MLPA.</div></div><div><h3>Results</h3><div><em>SMN1</em> exon 7 was deleted in 27% (58/214) of patients. Among those analyzed by MLPA (32/58), 75% (24/32) also carried an <em>SMN1</em> exon 8 deletion. <em>SMN2</em> exon 7 copy number ranged from 2 to 4, with lower copies correlating with greater disease severity. <em>NAIP</em> exon 5 deletion was primarily seen in type I SMA. Combined <em>SMN1</em>–<em>SMN2</em>–<em>NAIP</em> genotypes showed that 80% of type I patients (8/10) had 2 <em>SMN2</em> copies and 0 <em>NAIP</em>; 66.7% of type II (4/6) had 3 <em>SMN2</em> copies and ≥ 1 <em>NAIP</em>; and 75% of type III (12/16) had either 3 <em>SMN2</em> copies with 1–2 <em>NAIP</em> or 4 <em>SMN2</em> copies with variable <em>NAIP</em> status.</div></div><div><h3>Conclusions</h3><div>This study demonstrated an inverse correlation between <em>SMN2</em> and <em>NAIP</em> copy numbers and SMA severity. Combined <em>SMN1</em>–<em>SMN2</em>–<em>NAIP</em> genotypes provided stronger predictive insights on disease severity than individual gene copy number. Implementing CNV analysis of these genes in Morocco could enhance SMA severity prediction and support genetic counseling.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101299"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344724","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}

{"title":"Clinical implications of a novel SERPINA1 variant c.236 T > A: Challenges in characterizing new rare alpha-1 antitrypsin mutations","authors":"Arturo Olivares-Rivera ,&nbsp;Hilal Ersöz ,&nbsp;Philipp Höger ,&nbsp;Martina Veith ,&nbsp;Timm Greulich ,&nbsp;Kai Schlamp ,&nbsp;Sabina Janciauskiene ,&nbsp;Felix Herth ,&nbsp;Franziska C. Trudzinski","doi":"10.1016/j.ymgmr.2026.101295","DOIUrl":"10.1016/j.ymgmr.2026.101295","url":null,"abstract":"<div><div>Severe alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition characterized by low levels of alpha-1 antitrypsin (AAT), leading to progressive lung and/or liver disease. Most severe cases are linked to the Z allele (c.1096G &gt; A (p.Glu366Lys)) of the <em>SERPINA1</em> gene but characterizing patients with rare mutations remains challenging. This case report discusses the clinical significance of a novel <em>SERPINA1</em> variant, c.236 T &gt; A (p.Val79Glu; ClinVar accession SCV007334878), and the challenges in profiling such cases. Two male siblings carried both the common Z allele mutation and the novel exon 2 mutation. Despite genetic similarities, their clinical courses diverged. The older brother, a 66-year-old patient, presented with very severe airflow obstruction (GOLD stage IV) and an AAT level of 0.32 g/L. After years of pharmacologic treatment and endoscopic lung volume reduction, his condition worsened, requiring a double lung transplant. In contrast, the younger brother, currently 58 years old, was diagnosed through family screening and had an AAT level of 0.4 g/L. His condition progressed to panlobular basal emphysema accompanied by bronchopathy and mild bronchiectasis, managed with pharmacologic therapy. Both siblings had a history of smoking, potentially influencing their clinical outcomes. This case highlights the complexity of assessing rare <em>SERPINA1</em> mutations due to underlying biochemical complexities, genetic variability, and diagnostic limitations. It underscores the importance of combining biochemical analysis of variant AAT proteins with clinical evaluation to better understand disease expression, the value of genetic screening in family members, and the need for personalized clinical management to support timely and appropriate therapeutic interventions.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101295"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169979","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}

{"title":"Glycogen storage disease type IX: Long-term follow-up of 52 patients from three European countries","authors":"Martin Magner ,&nbsp;Robert Šáhó ,&nbsp;Petra Slavíková ,&nbsp;Radovan Bakaľár ,&nbsp;Lenka Dvořáková ,&nbsp;Karolína Pešková ,&nbsp;Danijela Petković Ramadža ,&nbsp;Ivo Barić ,&nbsp;Nikola Ilic ,&nbsp;Anna Čechová ,&nbsp;Martin Řeboun ,&nbsp;Hana Vlášková ,&nbsp;Silvie Kelifová ,&nbsp;Pavel Ješina ,&nbsp;Dagmar Procházková ,&nbsp;Hana Hansíková ,&nbsp;Tomáš Honzík ,&nbsp;Jiří Zeman","doi":"10.1016/j.ymgmr.2026.101297","DOIUrl":"10.1016/j.ymgmr.2026.101297","url":null,"abstract":"<div><div>Glycogen storage disease type IX (GSD IX) arises from hepatic phosphorylase b kinase (PhK) deficiency attributable to pathogenic variants in the PHKA2, PHKB, and PHKG2 genes. This multicenter retrospective study evaluated clinical and biochemical data from 52 patients diagnosed across three European countries, with a median follow-up of 9.3 years (range: 1–49). In the cohort, 86.5% were classified as GSD IXa, whereas GSD IXb and IXc accounted for 7.7% and 3.8%, respectively; one diagnosis was based solely on enzymatic testing. Null variants in PHKA2 consistently resulted in severe PhK deficiency, whereas missense variants and in-frame deletions were associated with variable enzymatic impairment (8/19 tested cases). The median age at symptom onset was 1.6 years, and the mean age at diagnosis was 2.0 years. Predominant manifestations included hepatomegaly (82%), elevated aminotransferases (81%), hypertriglyceridemia (71%), hypercholesterolemia (67%), hypoglycemia (46%), hyperlactatemia (38%), and short stature (30%). Aberrant apolipoprotein C-III glycosylation was detected in 80% of analyzed samples. Nutritional intervention was associated with improved growth (height SD score − 0.8 ± 1.3 vs −0.2 ± 1.65; <em>p</em> = 0.031) and fewer documented fasting hypoglycemia episodes (20/44 vs 9/44; <em>p</em> = 0.012), although hepatomegaly frequently persisted. Liver biopsies showed steatosis, fibrosis, and/or chronic hepatitis in 52% of examined cases. A single hepatic adenoma was identified in a 14-year-old male. Overall, the clinical course of GSD IX was favorable, with hepatomegaly, elevated liver enzymes, and dyslipidemia as the most prevalent features. Severe hypoglycemic episodes were uncommon, and no clear genotype–phenotype correlation emerged.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101297"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276786","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}

{"title":"Unveiling alpha-mannosidosis in Iraqi children: A series of clinically and genetically characterized cases with novel MAN2B1 variant","authors":"Mays Riyadh Al Tai ,&nbsp;Nebal Waill Saadi ,&nbsp;Marwa Sabah Alothman ,&nbsp;Ikhlas Ali Ahmed ,&nbsp;Hala Sameh Arif ,&nbsp;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 &gt; 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":"2026-03-01","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}

{"title":"Two adult sisters with untreated phenylketonuria: Strikingly discordant clinical phenotype","authors":"Didem Demirbas,&nbsp;Susan E. Waisbren,&nbsp;Olaf Bodamer,&nbsp;Christina Y. Hung,&nbsp;Farrah Rajabi ,&nbsp;Gerard Berry,&nbsp;Harvey L. Levy","doi":"10.1016/j.ymgmr.2026.101304","DOIUrl":"10.1016/j.ymgmr.2026.101304","url":null,"abstract":"<div><div>Intellectual disability is the cardinal clinical feature of untreated phenylketonuria (PKU). Nevertheless, there are rare individuals with untreated PKU who have had normal or near normal cognition despite having never been treated. We are reporting two adult sisters with untreated PKU who are strikingly discordant in cognition and the studies we conducted to determine whether there is a significant difference between the sisters that might explain the discordancy. The older sister has the expected moderate to severe cognitive disability while the younger sister is intellectually normal having graduated from college and serving as an executive secretary until retirement. Studies that include plasma phenylalanine (Phe) and other amino acids, urine organic acids, phenylalanine hydroxylase (<em>PAH</em>) genotype, <em>in vivo</em> PAH activity, brain MRI, and whole exome sequencing failed to reveal a significant difference between the sisters. The results of published studies comparing cognitively normal and abnormal individuals with untreated PKU also failed to reveal a significant difference with the exception of a single unconfirmed study reporting a lower brain Phe level in three adults with untreated PKU (Moller HE, Weglage J, Wiedermann D, Ullrich K, 1998). It is important to identify and study cognitively normal or near normal individuals with untreated PKU in search of a factor that might explain the discordancy in clinical outcome and lead to a further understanding of pathogenesis in PKU.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101304"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397688","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}

{"title":"Newborn screening, genetic analysis, and long-term follow-up of 89 cases with short-chain acyl-CoA dehydrogenase deficiency (SCADD)","authors":"GuLing Qian ,&nbsp;Chen Liu ,&nbsp;YanHua Xu ,&nbsp;Duo Zhou ,&nbsp;Chi Chen ,&nbsp;BenQing Wu ,&nbsp;XinWen Huang","doi":"10.1016/j.ymgmr.2026.101292","DOIUrl":"10.1016/j.ymgmr.2026.101292","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to delineate the neonatal screening landscape, incidence, tandem mass spectrometry (MS/MS)-based metabolic signatures, ACADS gene variant spectrum, and long-term clinical outcomes of short-chain acyl-CoA dehydrogenase deficiency (SCADD) in newborns from Zhejiang Province, China.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted on 4,667,883 newborns in Zhejiang screened between November 2013 and August 2025. Acylcarnitine profiles in dried blood spots were analyzed by MS/MS. Urinary organic acids and ACADS gene variants were detected via gas chromatography–mass spectrometry (GC–MS) and high-throughput sequencing, respectively. Confirmed SCADD patients underwent longitudinal follow-up to evaluate growth, neurodevelopment, and biochemical parameters.</div></div><div><h3>Results</h3><div>Initial screening identified 500 infants with elevated butyrylcarnitine (C4) or C4/ propionylcarnitine (C3) ratios; 89 were confirmed as SCADD, corresponding to an incidence of 1 in 52,448 (1.9 per 100,000). All patients were asymptomatic during the neonatal period. Among the 26 patients who underwent urinary GC/MS, 25 (96.2%) presented with elevated ethylmalonic acid (EMA) levels. Fifty-one ACADS variants were identified, with missense variants (46/51, 90.2%) being the most prevalent; the top three variants were c.1031 A &gt; G (28.1%), c.164C &gt; T (13.5%), and c.1130C &gt; T (11.2%).</div></div><div><h3>Conclusions</h3><div>The incidence of SCADD in Zhejiang is 1 in 52,448, with c.1031 A &gt; G and c.164C &gt; T as the most frequent ACADS variants; and most screen-detected SCADD cases remain asymptomatic.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101292"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169977","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}

{"title":"Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report","authors":"Wiebke Hahn ,&nbsp;Karla Erffmeier ,&nbsp;Maximilian Schulze ,&nbsp;Felix Zahnert ,&nbsp;Susanne Knake ,&nbsp;Panagiota-Eleni Tsalouchidou","doi":"10.1016/j.ymgmr.2026.101296","DOIUrl":"10.1016/j.ymgmr.2026.101296","url":null,"abstract":"<div><h3>Background</h3><div>Mutations in COQ8A cause primary coenzyme Q10 deficiency, which can present clinically heterogeneously: Symptoms range from cerebellar ataxia, epilepsy, encephalomyopathy, macular degeneration to nephropathy. High-dose coenzyme Q10 supplementation is widely used, yet there is little evidence on complementary strategies, particularly for non-epileptic features such as cerebellar ataxia.</div></div><div><h3>Case presentation</h3><div>We report a 46-year-old female with genetically confirmed COQ8A-related coenzyme Q10 (CoQ10) deficiency, presenting with ataxia and epilepsy characterized by myoclonic and bilateral tonic–clonic seizures, who participated in a clinical protocol of ketogenic intermittent fasting, a method of intermittent fasting combined with medium-chain triglycerides (MCT) primarily designed for seizure management. The patient followed a 16:8 intermittent fasting regime combined with MCT intake for three months, followed by three months of all-alone intermittent fasting. Routine blood markers and brain MRI, including diffusion imaging were obtained before and after ketogenic fasting.</div></div><div><h3>Results</h3><div>During the study protocol, while no seizure reduction in myoclonic seizures could be observed, ataxia - quantified by the Scale for the Assessment and Rating of Ataxia (SARA) - improved significantly from 8.5 to 6.0 during the interventions. MRI showed a trend suggesting improved cerebellar microstructural integrity.</div></div><div><h3>Conclusions</h3><div>This case highlights the potential of ketogenic intermittent fasting as an adjunct therapy for mitochondrial ataxia. Ketogenic intermittent fasting was associated with clinically meaningful improvement of ataxia in a patient with COQ8A-related CoQ10 deficiency, suggesting that ketogenic dietary strategies may represent a promising adjunct therapeutic approach for mitochondrial ataxia. Future research should assess this intervention in larger patient cohorts to confirm its potential benefits.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101296"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169978","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}

{"title":"Olipudase alfa treatment for pediatric acid sphingomyelinase deficiency in Egypt: A prospective, observational cohort study with an interventional subgroup","authors":"Nehal Abdelaziz Arafa ,&nbsp;Aml Mahfouz ,&nbsp;Shimaa Anwar ,&nbsp;Iman Marzouk","doi":"10.1016/j.ymgmr.2026.101293","DOIUrl":"10.1016/j.ymgmr.2026.101293","url":null,"abstract":"<div><h3>Objectives</h3><div>To present key features of pediatric acid sphingomyelinase deficiency (ASMD) and assess the clinical and safety outcomes of enzyme replacement therapy with olipudase alfa.</div></div><div><h3>Study design</h3><div>A prospective, observational cohort study of pediatric patients with ASMD that included an interventional subgroup treated with olipudase alfa. Patients presenting to the Alexandria University Children's Hospital in Egypt from June 2022 to May 2023 underwent clinical examination and genetic testing. Clinical and safety outcomes were assessed in patients who received biweekly infusions of olipudase alfa for 12 months.</div></div><div><h3>Results</h3><div>Fifteen pediatric patients with ASMD were included (10 were classified as type A or A/B and 5 were classified as type B). Patients with ASMD type A or A/B presented earlier and more severely, with a higher rate of mortality than patients with type B. Qualitative improvements in developmental and neurocognitive outcomes, clinical presentation, and laboratory parameters were observed among the patients with ASMD type A/B or type B treated with olipudase alfa (<em>n</em> = 6), with only mild safety events recorded. Treated patients with type B (<em>n</em> = 4) demonstrated significantly improved weight (<em>p</em> = 0.031, <em>η</em>² = 0.757) and height/length <em>Z</em>-scores (<em>p</em> = 0.009, <em>η</em>² = 0.707), and liver size (<em>p</em> = 0.025, <em>η</em>² = 0.839) compared with baseline.</div></div><div><h3>Conclusions</h3><div>This case series contributes to the clinical and biochemical understanding of ASMD and may help reduce diagnostic delays and improve clinical management. Olipudase alfa was generally well tolerated, and promising clinical improvements were observed.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101293"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169976","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}

{"title":"Molecular characterization of Alkaptonuria in Brazilian patients","authors":"Carolina Araújo Moreno ,&nbsp;Ruy Pires de Oliveira Sobrinho ,&nbsp;Josep Jorente ,&nbsp;Simone Appenzeller ,&nbsp;Nelma Gláucia Silva Meira ,&nbsp;Lucas Cadete Caldeira Costa ,&nbsp;Angelina Xavier Acosta ,&nbsp;The Brazilian Rare Genomes Project Consortium ,&nbsp;Mara Sanches Guaragna ,&nbsp;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 &gt; T and c.899 T &gt; 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 &gt; 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 &gt; A and c.899 T &gt; G in one individual, and deletion of exon 13 of the <em>HGD</em> gene in trans with the c.1007-172 A &gt; 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 &gt; 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":"2026-03-01","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}

{"title":"Identification of Multiple Sulfatase Deficiency (MSD) in newborn screening: A case study","authors":"Taraka R. Donti,&nbsp;James C. DiPerna,&nbsp;Madhuri R. Hegde,&nbsp;Revvity Omics, Inc","doi":"10.1016/j.ymgmr.2025.101285","DOIUrl":"10.1016/j.ymgmr.2025.101285","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101285"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897979","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}