Molecular Genetics and Metabolism Reports最新文献

{"title":"A study of Iraqi patients with homocysteine remethylation disorders in a tertiary pediatric centre","authors":"Mays R. Al-Tai ,&nbsp;Adel A. Kareem ,&nbsp;Nebal W. Saadi ,&nbsp;Tawfig Ben Omran ,&nbsp;Ban A. Abdul Majeed ,&nbsp;Ibrahim F. Ibrahim ,&nbsp;Lamia A. Alattar","doi":"10.1016/j.ymgmr.2025.101217","DOIUrl":"10.1016/j.ymgmr.2025.101217","url":null,"abstract":"<div><h3>Background</h3><div>Hyperhomocysteinemia is a group of inherited homocysteine metabolism disorders characterised by elevated blood homocysteine levels (total homocysteine &gt;15 μM). Homocystinuria is classified into two main homocysteine metabolism disorders. Classical Homocystinuria is caused by a deficiency of the pyridoxine-dependent enzyme cystathionine beta-synthase in the trans‑sulfuration pathway. Non-classical Homocystinuria is a group of disorders affecting the interconversion of methionine to homocysteine through the re-methylation pathway.</div></div><div><h3>Aim</h3><div>This study aims to describe the clinical, biochemical, and genetic profiles of patients with re-methylation disorders.</div></div><div><h3>Patients and methods</h3><div>A cohort study was conducted at the metabolic clinic of Children Welfare Teaching Hospital in Baghdad from the 1st of December 2021 to the 1st of December 2022. The study included fifteen patients who met the following criteria: (1) elevated serum homocysteine levels (&gt;15 μmol/L); (2) low or normal blood methionine levels (12–40 μmol/L). <strong>Results:</strong> fourteen MTHFR patients underwent statistical analysis, and one CblC patient was assessed separately. MTHFR patients comprised nine females and five males. The mean age at presentation was 7.1 years ±4.5, ranging from 1 to 16 years. Consanguineous marriages were reported in 13 patients. A family history of a similar disorder was documented in 73 % of cases. Among the families, four had two affected siblings. The two main reported clinical manifestations were gait disturbance (10/14, 71.4 %) and cognitive impairment/intellectual disability (6/14, 42.8 %). Brain MRI was conducted for all studied patients, with leukodystrophy being the most common finding (8/14, 57.1 %). Molecular testing revealed variants in <em>MTHFR</em> in 14 patients, and <em>MMACHC</em> in one patient.</div></div><div><h3>Conclusion</h3><div>According to this study, individuals with homocysteine re-methylation disorders can manifest symptomatology such as neuroregression, psychomotor delay, and whiter matter changes earlier than anticipated. And these disorders are amenable to treatment. Genetic testing is crucial in identifying the specific mutation type and guiding definitive treatment.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101217"},"PeriodicalIF":1.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817547","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":"Cardiac manifestations in adult patients with inherited metabolic disease: A single-center experience","authors":"Flutura Sadiku ,&nbsp;Tobias Rutz ,&nbsp;Andrea Superti-Furga ,&nbsp;Pierre Monney ,&nbsp;Christel Tran","doi":"10.1016/j.ymgmr.2025.101216","DOIUrl":"10.1016/j.ymgmr.2025.101216","url":null,"abstract":"<div><h3>Background</h3><div>Inherited metabolic diseases (IMDs) can affect the heart, but data on cardiac manifestations in adults are scarce. This study examines the clinical and radiological features of cardiac complications in adults with IMDs.</div></div><div><h3>Methods</h3><div>This retrospective study included adult patients at our metabolic clinic with a biochemical and/or genetic diagnosis of IMD who underwent cardiac investigations. Records were reviewed for clinical features, echocardiograms, electrocardiograms, and treatment. Patients were categorized into three IMD subgroups: disorders of small molecules, complex molecules, and energy production.</div></div><div><h3>Results</h3><div>Of the 115 adult patients with IMD, 48 underwent cardiac testing (mean age 39.1 ± 14.8 years). Abnormal cardiac findings were reported in 23 of these patients (47.9 %, 14 men). Five (21.7 %) were symptomatic with dyspnea, peripheral edema, or chest pain. Fourteen patients (60.9 %) had heart muscle disease, 6 (26.1 %) had valvular involvement, and 5 (21.7 %) had arrhythmia. Valvular and heart muscle disease predominated in complex and small molecule disorders (3/4 and 7/9 respectively). Energy production disorders showed mixed involvement: heart muscle disease (5/10) and arrhythmia (5/10). Twelve of the 23 patients with abnormal findings (52.2 %) received specific cardiac therapy. All but one patient remained stable under treatment.</div></div><div><h3>Discussion</h3><div>In this cohort, cardiac disease was diagnosed in 23 of 115 adults with IMD (20 %), including structural heart defects and arrhythmia. The pattern and severity of cardiac involvement varied between disorders, with arrhythmia mainly associated with energy production disorders. Outcomes were favorable in most cases, likely due to collaboration between metabolic physicians and cardiologists and timely follow-up and treatment.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101216"},"PeriodicalIF":1.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817549","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":"Disease profile in a cohort of Brazilian patients diagnosed with alpha-mannosidosis","authors":"Fabiano de Oliveira Poswar ,&nbsp;Tamires Silva Alves ,&nbsp;Daniel Rocha de Carvalho ,&nbsp;Hélio van der Linden Jr ,&nbsp;Charles Marques Lourenço ,&nbsp;Dafne Dain Gandelman Horovitz ,&nbsp;Anneliese Barth ,&nbsp;Carmen Silvia Curiati Mendes ,&nbsp;Ana Maria Martins ,&nbsp;Roberto Giugliani","doi":"10.1016/j.ymgmr.2025.101220","DOIUrl":"10.1016/j.ymgmr.2025.101220","url":null,"abstract":"<div><div>Alpha-mannosidosis (AM) is an ultrarare multisystemic disorder caused by alpha-mannosidase deficiency. This is the first comprehensive report on AM in Brazil, analyzing clinical and laboratory data from 14 patients diagnosed between 2001 and 2021. We summarize the patient diagnostic journey in the country, including the most common presenting symptoms, the time from disease onset to diagnosis and discuss other disease manifestations. Our findings may improve the disease awareness and understanding in the country.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101220"},"PeriodicalIF":1.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817550","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 decades of experience of the Fabry Outcome Survey provides further confirmation of the long-term effectiveness of agalsidase alfa enzyme replacement therapy","authors":"Uma Ramaswami ,&nbsp;Guillem Pintos-Morell ,&nbsp;Christoph Kampmann ,&nbsp;Kathleen Nicholls ,&nbsp;Dau-Ming Niu ,&nbsp;Ricardo Reisin ,&nbsp;Michael L. West ,&nbsp;Christina Anagnostopoulou ,&nbsp;Jaco Botha ,&nbsp;Dalia Jazukeviciene ,&nbsp;Jörn Schenk ,&nbsp;Derralynn A. Hughes ,&nbsp;Roberto Giugliani","doi":"10.1016/j.ymgmr.2025.101215","DOIUrl":"10.1016/j.ymgmr.2025.101215","url":null,"abstract":"<div><h3>Background</h3><div>Analyses of up to 20 years of data from the Fabry Outcome Survey (FOS) assessed the long-term effectiveness of agalsidase alfa enzyme replacement therapy.</div></div><div><h3>Methods</h3><div>The impact of agalsidase alfa treatment on renal, cardiac, morbidity, and mortality outcomes in FOS was compared with untreated external Fabry disease (FD) cohorts.</div></div><div><h3>Results</h3><div>A total of 2171 FOS patients (1014 men, 919 women, 163 boys, 75 girls) received agalsidase alfa (median [range] duration of treatment: 5.38 [0.0–20.8] years). Annual rates of decline in estimated glomerular filtration rate improved in treated patients versus untreated external cohorts regardless of sex or baseline urinary protein levels. Annual left ventricular mass index rates were stable in treated patients regardless of sex or baseline left ventricular hypertrophy status, and better than in untreated external cohorts. The mean age at which 50 % of patients had their first composite morbidity event was later in the agalsidase-alfa-treated population than in the untreated external cohort (51.7 vs 41 years [males]; 60.8 vs 53 years [females]). After 24 months of treatment, the probability of a composite morbidity event was ∼34 % in treated patients and ∼ 45 % in untreated patients. Treated patients were older at death than untreated patients (mean [range]: 61.7 [26.2–87.6] vs 50.3 [34.5–70.1] years). The mean age at which 50 % of male patients were still alive was higher in treated patients than in untreated external cohorts (75.5 vs 60.0 years).</div></div><div><h3>Conclusions</h3><div>Long-term treatment with agalsidase alfa may provide renal, cardiac, and overall survival protection in FD.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101215"},"PeriodicalIF":1.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817548","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":"Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review","authors":"Etienne Mondésert ,&nbsp;Juliette Bouchereau ,&nbsp;Manuel Schiff ,&nbsp;Jean-François Benoist ,&nbsp;Guilia Barcia ,&nbsp;Boris Keren ,&nbsp;Inès Mannes ,&nbsp;Clément Pontoizeau ,&nbsp;Charlotte Mansat ,&nbsp;Apolline Imbard","doi":"10.1016/j.ymgmr.2025.101213","DOIUrl":"10.1016/j.ymgmr.2025.101213","url":null,"abstract":"<div><div>Branched-chain amino acid transferase type 2 (BCAT2) deficiency is a rare autosomal recessive genetic condition, with only seven cases described to date. It results in an elevation of branched-chain amino acid (BCAA) plasma concentrations, predominantly on valine, with normal concentration of plasma allo-isoleucine and urine branched-chain α-keto acids (BCKA). Despite this constant biochemical feature, clinical consequences remain unclear with heterogeneous and far less severe than maple syrup urine disease (MSUD) reported phenotypes, one individual being even asymptomatic.</div><div>We report herein the eighth case of genetically confirmed BCAT2 deficiency, accompanied by a literature review and a discussion about the potential pathogenicity of this condition.</div><div>An 11-year-old boy presented with a rapidly reversible initial acute neurological episode suggesting an epileptic seizure. Abnormalities on cerebral magnetic resonance imaging and suspicion of cognitive impairment led to further metabolic investigations. BCAT2 deficiency has been mentioned in front of increased BCAAs (valine = 1667 μmol/L, leucine = 701 μmol/L, isoleucine = 561 μmol/L). A homozygous novel nonsense variant on <em>BCAT2</em> (c.34C &gt; T, p.Arg12*) was found on whole exome sequencing. After oral pyridoxine supplementation (200 mg/day), a decrease in BCAA concentrations was observed (valine = 984 μmol/L, leucine = 462 μmol/L, isoleucine = 302 μmol/L).</div><div>Laboratory and imaging findings were consistent with previously reported cases. However, clinical presentation of this case was atypical and could be related with epilepsy, although no other variant on epilepsy genes have been found. The relation between BCAT2 deficiency and these clinical findings is at this stage debated with regard to phenotypic variability. Further case-studies are needed to expand the knowledge about this condition.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101213"},"PeriodicalIF":1.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799309","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":"The recurrent p.Glu3Lys variant in EHHADH is responsible for Fanconi syndrome with early liver dysfunction and mitochondrial abnormalities","authors":"P. Rollier ,&nbsp;A. Cospain ,&nbsp;M. Barth ,&nbsp;V. Milon ,&nbsp;N. Gueguen ,&nbsp;C. Homedan ,&nbsp;V. Desquiret ,&nbsp;C. Bris ,&nbsp;E. Colin ,&nbsp;L. Damaj ,&nbsp;A. Ryckewaert ,&nbsp;P. Reynier ,&nbsp;S. Odent ,&nbsp;P. Amati-Bonneau ,&nbsp;V. Procaccio ,&nbsp;D. Bonneau ,&nbsp;A. Ziegler","doi":"10.1016/j.ymgmr.2025.101214","DOIUrl":"10.1016/j.ymgmr.2025.101214","url":null,"abstract":"<div><h3>Background</h3><div>The recurrent pathogenic variant c.7G&gt;A p.Glu3Lys in the <em>EHHADH</em> gene is responsible for an autosomal dominant form of Fanconi renotubular syndrome. This variant leads to mislocalization of peroxisomal EHHADH protein to the mitochondria, thereby impairing mitochondrial function. To date, this variant has been reported in only two unrelated families, with affected individuals presenting with isolated renotubular Fanconi syndrome. No other pathogenic variant has been documented in this gene.</div></div><div><h3>Methods</h3><div>A boy followed from four months-old to twelve years-old underwent clinical evaluation, mitochondrial analyses and exome sequencing.</div></div><div><h3>Results</h3><div>The four-month-old infant boy presented with hypoglycemia, ketonuria, lactic acidosis and hepatic cytolysis. Three months later, a Fanconi tubulopathy with nephrocalcinosis appeared. Mitochondrial respiratory chain analyses performed on hepatocytes showed a decreased activity of complex I and IV of the mitochondrial respiratory chain and a quantitative decrease of these complexes. Exome sequencing revealed the missense variant c.7G&gt;A p.Glu3Lys, inherited from his father who was asymptomatic at 54 years old. A diet supplemented in medium-chain fatty acids was experimented.</div></div><div><h3>Conclusion</h3><div>This case widens the phenotypic spectrum of the recurrent p.Glu3Lys variant in <em>EHHADH</em>, which may be responsible for Fanconi syndrome and early onset hepatic dysfunction with cytolysis and hypoglycemia. Medium-chain fatty acids supplemented diet did not improve the disease.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101214"},"PeriodicalIF":1.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768681","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":"Outcome of creatine supplementation therapy in phosphoglucomutase-1 deficiency associated congenital disorders of glycosylation: Novel insights","authors":"Anastasia Ambrose ,&nbsp;Morganne McCabe ,&nbsp;Clara Hung ,&nbsp;Iveta Sosova ,&nbsp;Peter Seres ,&nbsp;Saadet Mercimek-Andrews","doi":"10.1016/j.ymgmr.2025.101212","DOIUrl":"10.1016/j.ymgmr.2025.101212","url":null,"abstract":"<div><h3>Background</h3><div>Biallelic pathogenic variants in <em>PGM1</em> result in phosphoglucomutase 1 (PGM1) deficiency that is one of the congenital disorders of glycosylation (CDG) (PGM1-CDG). Phenotypic spectrum includes congenital malformations, and muscular, cardiac, hepatic, endocrine and hematologic phenotypes. Current treatment consists of D-galactose therapy that results in clinical and biochemical improvements. To improve fatigue, and exercise intolerance, we started creatine supplementation therapy.</div></div><div><h3>Material and methods</h3><div>We reviewed electronic patient chart. We applied Nijmegen Pediatric CDG Rating Scale (NPCRS) and The Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F). We measured creatine metabolism biomarkers.</div></div><div><h3>Results</h3><div>This is a 29-year-old female with PGM1-CDG, confirmed diagnosis by clinical exome sequencing. She has been treated with D-galactose therapy which did not improve her fatigue and exercise intolerance. She was started on creatine supplementation therapy at the age of 27 years which led to decreased daytime sleeping, increased exercise capacity and improvements in her NPCRS, and FACIT-F. Her plasma guanidinoacetate was low. She had elevated urine galactitol on D-galactose therapy.</div></div><div><h3>Discussion</h3><div>PGM1-CDG associated myopathy is likely due to combination of several factors including abnormal muscle carbohydrate metabolism, abnormal N-glycosylation of proteins involved in the muscle functions and creatine transport and altered muscle energy homeostasis. It was previously shown that creatine supplementation therapy improves myopathy in patients with mitochondrial cytopathies. We think that the use of creatine supplementation therapy coincided with improvements in fatigue and exercise intolerance subjectively and objectively in our patient.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101212"},"PeriodicalIF":1.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768682","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":"Benefits of early intervention with olipudase alfa in symptomatic children with acid sphingomyelinase deficiency: A sibling case-comparison study","authors":"Drew B. Sinha ,&nbsp;William L. Simpson ,&nbsp;Andrew Ting ,&nbsp;Louise Bier ,&nbsp;Mary Freeman ,&nbsp;Lauren Mackenzie Mason ,&nbsp;George A. Diaz ,&nbsp;Jaya Ganesh","doi":"10.1016/j.ymgmr.2025.101210","DOIUrl":"10.1016/j.ymgmr.2025.101210","url":null,"abstract":"<div><div>Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multisystem complications including neurodegeneration, hepatosplenomegaly, interstitial lung disease (ILD), bone marrow disease, and growth failure. Non-neurological manifestations of this disease are amenable to enzyme replacement therapy (ERT) with olipudase alfa in both adult and pediatric patients. In this study, we offer evidence for the role of intervention in early childhood pediatric cases. We present longitudinal follow-up for two siblings with ASMD (<em>SMPD1</em> p.R498L/p.R610del compound heterozygous genotype) who were started on ERT at different ages (ages 3 and 7, duration of treatment &gt;4 years). After initiation of ERT, both siblings demonstrated significant radiographic improvement of interstitial lung disease (ILD), organomegaly, and growth. Notably, the younger sibling who had started earlier on treatment did not experience any deceleration in growth parameters and has normal height and weight for age, while the older sibling showed a decline in growth velocity that improved once treatment was initiated. Similarly, the older sibling showed similar-to-worse ILD and more persistent organomegaly compared to the younger sibling. Treatment has resulted in sustained improvements in both patients. These findings suggest that early intervention with ERT in ASMD may have cumulative benefits for pediatric health and motivate early screening for ASMD in pediatric patients.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101210"},"PeriodicalIF":1.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759504","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":"Atypical case of neonatal-onset Gaucher disease type 3b: A case report","authors":"Takanori Onuki ,&nbsp;Kinuko Kojima ,&nbsp;Kentaro Sawano ,&nbsp;Nao Shibata ,&nbsp;Yohei Ogawa ,&nbsp;Go Hasegawa ,&nbsp;Aya Narita ,&nbsp;Hiromi Nyuzuki","doi":"10.1016/j.ymgmr.2025.101211","DOIUrl":"10.1016/j.ymgmr.2025.101211","url":null,"abstract":"<div><div>Neonatal-onset Gaucher disease (nGD) is considered perinatal lethal GD, a variant of GD type 2 (GD2), and is associated with collodion skin or hydrops fetalis, hepatosplenomegaly, and involvement of central nervous system (CNS). Pulmonary involvement (PI) and lymphadenopathy (LD) are reported GD complications and have unknown incidence, pathogenesis, and response to treatments. Here, we report the case of a patient diagnosed with nGD with collodion skin who developed only mild neurological symptoms and later died in early childhood due to treatment-resistant PI and LD. A female neonate was born at 38 weeks of gestation (weight: approximately 2012 g, height: 45 cm). She had a collodion skin, hepatosplenomegaly, hemorrhagic plaques, and cholestatic liver disease at birth. She was diagnosed with GD based on decreased glucocerebrosidase enzyme activity, and genetic analysis of <em>GBA1</em> revealed compound heterozygous mutations of c.1193G &gt; T (p.Arg398Leu) and c.1265_1319del (p.Leu422fs). Intravenous enzyme replacement therapy (ERT) was initiated at the 15 days of age. At the age of 2 years and 2 months, she had a Developmental Quotient of 88 but developed horizontal gaze palsy. At 2 years 8 months of age, she developed mesenteric LD and PI because of which she failed to gain weight and developed tachypnea. She was started on oxygen therapy but died of respiratory failure and malnutrition due to PI and LD at the age of 3 years and 8 months. Pathological autopsy did not reveal the presence of Gaucher cells (GCs) in the liver, spleen, and bone marrow, but all lung macrophages had been transformed to GCs that were draining the alveoli, LD was observed in the mesenteric and mediastinal lymph nodes, and nodules of GCs were formed in bilateral kidneys. In conclusion, nGD with collodion skin is not always classified GD2. Although her phenotype may be classified as GD3b, her clinical course was like severe GD1. In addition, PI and LD are difficult to treat with adequate ERT.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101211"},"PeriodicalIF":1.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735014","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":"The precise molecular diagnosis of novel GLDC compound heterozygous variants highlights the benefits for a Chinese family with nonketotic hyperglycinemia","authors":"Fang Yuan ,&nbsp;Xiaozhen Song ,&nbsp;Rongrong Yin ,&nbsp;Xiaoping Lan ,&nbsp;Jingjing Sun ,&nbsp;Xiaojun Tang ,&nbsp;Wuhen Xu ,&nbsp;Shaohua Hu ,&nbsp;Man Xiao ,&nbsp;Hong Zhang ,&nbsp;Wenhao Weng ,&nbsp;Yuanfeng Zhang ,&nbsp;Shengnan Wu","doi":"10.1016/j.ymgmr.2025.101209","DOIUrl":"10.1016/j.ymgmr.2025.101209","url":null,"abstract":"<div><div>Glycine encephalopathy, also known as nonketotic hyperglycinemia (NHK), is a rare inherited disease caused by an inborn error of glycine metabolism, resulting in elevated glycine concentration in plasma and cerebrospinal fluid. Clinical manifestations mainly include varying degrees of hypotonia, apneic episodes, epilepsy, psychomotor delay during the neonatal period or early infancy. Biallelic variants in <em>GLDC</em> account for up to 80 % of classical NKH cases. Here we describe the clinical, biochemical, and molecular characteristics of two Chinese siblings with severe NHK. Their phenotypes included severe symptoms in neonatal period, seizures, and psychomotor delay. The siblings carry novel compound heterozygous variants in <em>GLDC</em>, c.1740C &gt; G (p.His580Gln) and c.1023G &gt; A (p.Val341=). Based on previous literature reports and pathogenicity prediction, the c.1740C &gt; G (p.His580Gln) variant is classified as likely pathogenic. By minigene analysis, we confirmed the synonymous mutation c.1023G &gt; A (p.Val341=) led to abnormal splicing, with 38 bp missing in exon 7 in the <em>GLDC</em> gene. These findings highlight the pathogenic nature of a novel synonymous mutation c.1023G &gt; A, expand the genetic spectrum of <em>GLDC</em> and provide crucial guidance for both the patient's clinical management and family's reproductive genetic counseling.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101209"},"PeriodicalIF":1.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696807","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}