JIMD reports最新文献_第6页

Clinical Outcomes and Correlation With Biochemical Control in Hydroxocobalamin-Treated Patients With Early-Onset Cobalamin C Disease. 羟基钴胺治疗早发性钴胺C病患者的临床结局及其与生化控制的相关性

IF 1.8

JIMD reports Pub Date : 2026-04-27 eCollection Date: 2026-05-01 DOI: 10.1002/jmd2.70091

Arthavan Selvanathan, Ashley Hertzog, Jacqui Russell, Rosie Junek, Carolyn Ellaway, Kate Lichkus, Adviye Ayper Tolun, Kaustuv Bhattacharya

{"title":"Clinical Outcomes and Correlation With Biochemical Control in Hydroxocobalamin-Treated Patients With Early-Onset Cobalamin C Disease.","authors":"Arthavan Selvanathan, Ashley Hertzog, Jacqui Russell, Rosie Junek, Carolyn Ellaway, Kate Lichkus, Adviye Ayper Tolun, Kaustuv Bhattacharya","doi":"10.1002/jmd2.70091","DOIUrl":"10.1002/jmd2.70091","url":null,"abstract":"Cobalamin C (cblC) disease is the most common disorder of Vitamin B12 activation. The early-onset form presents within the first few months of life, with some patients identified through newborn screening (NBS). However, despite early detection and optimal treatment, patient outcomes remain poor, with intellectual impairment and progressive visual loss in the majority. We reviewed a cohort of 10 patients with cblC disease, all identified either by NBS or a neonatal clinical presentation. We reviewed their biochemical control and correlated this with clinical progress and treatment. The majority of the cohort (including four asymptomatic patients) was identified through NBS and had genotypes predictive of early-onset disease. Clinical outcomes improved with standard-of-care treatment (hydroxocobalamin, betaine, and folinic acid) but were suboptimal, with both neurocognitive (6/10) and ophthalmological manifestations (10/10) occurring in most patients. One patient died at 5 months of age, and it is unclear whether this was related to cblC disease or not. Across over 250 timepoints from 9 patients, there was minimal correlation between cumulative intramuscular hydroxocobalamin (OHCbl) dose and biomarkers, including methylmalonic acid (r 2 = 0.0031) and total homocysteine (r 2 = 0.2858) levels. This study provides comprehensive, longitudinal biochemical, and clinical follow-up of patients with cblC disease treated from soon after birth, often presymptomatically. Our findings corroborate previous observations regarding the lack of correlation of current biomarkers, both with disease progression and with standard (< 0.3 mg/kg/day) hydroxocobalamin dosing. Further investigation of the clinical impact of early high-dose OHCbl treatment is needed in larger cohorts of patients.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 ","pages":"e70091"},"PeriodicalIF":1.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1.8

JIMD reports Pub Date : 2026-04-27

引用次数: 0

IF 1.8

JIMD reports Pub Date : 2026-04-24

引用次数: 0

Antenatal Presentation of MRPS22-Related Mitochondrial Disease Confirmed With Rapid Proteomics. 快速蛋白质组学证实mrps22相关线粒体疾病的产前表现

IF 1.8

JIMD reports Pub Date : 2026-04-24 eCollection Date: 2026-05-01 DOI: 10.1002/jmd2.70092

Liana N Semcesen, Megan Ball, Daniella H Hock, Juliet Kaye, Aimee Woods, Lucas De Jong, John Christodoulou, David R Thorburn, Alison G Compton, David A Stroud, Jan Liebelt

{"title":"Antenatal Presentation of MRPS22-Related Mitochondrial Disease Confirmed With Rapid Proteomics.","authors":"Liana N Semcesen, Megan Ball, Daniella H Hock, Juliet Kaye, Aimee Woods, Lucas De Jong, John Christodoulou, David R Thorburn, Alison G Compton, David A Stroud, Jan Liebelt","doi":"10.1002/jmd2.70092","DOIUrl":"10.1002/jmd2.70092","url":null,"abstract":"MRPS22-related mitochondrial disease (MIM#611719) is a rare autosomal recessive disorder caused by defects in the mitochondrial ribosomal protein S22, a component of the small mitoribosomal subunit essential for mitochondrial translation. Of the few reported cases, most present antenatally with a severe phenotype, conveying a poor prognosis. We describe a fetus with severe antenatal-onset MRPS22-related mitochondrial disease and the use of multi-omics in the molecular diagnosis. A primigravida underwent termination of pregnancy following identification of multiple congenital anomalies (hydrops fetalis, microcephaly, corpus callosal agenesis, periventricular cysts and cardiac hypertrophy) on ultrasound at 20 + 2 weeks' gestation, confirmed on fetal magnetic resonance imaging. Trio genome sequencing revealed compound heterozygous variants in MRPS22 (NM_020191.4: c.509G>A; p.(Arg170His) and c.565C>G; p.(Arg189Gly)). Rapid proteomic analysis demonstrated destabilisation of the small mitoribosomal subunit and combined reduction of OXPHOS complexes, supporting the pathogenicity of the variants. This case consolidates the antenatal phenotype of severe MRPS22-related disease and highlights the importance of considering mitochondrial disease in the differential diagnosis of congenital anomalies, especially hydrops fetalis and corpus callosum anomalies. This study provides evidence for the utility of multi-omic approaches (trio genome sequencing, proteomics) in confirming variant pathogenicity following pregnancy loss, enabling accurate diagnosis, and informing reproductive counselling for affected families.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 ","pages":"e70092"},"PeriodicalIF":1.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1.8

JIMD reports Pub Date : 2026-04-24

引用次数: 0

Should PNPO Deficiency Be Treated In Utero? Clinical Findings From Prenatal Pyridoxine Therapy. PNPO缺乏应该在子宫内治疗吗？产前吡哆醇治疗的临床表现。

IF 1.8

JIMD reports Pub Date : 2026-04-20 eCollection Date: 2026-05-01 DOI: 10.1002/jmd2.70086

Chloé de Puyraimond, Samia Pichard, Muriel Girard, Julian Delanne, Laurence Faivre, Apolline Imbard, Amandine Baurand, Jean-François Benoist, Philippa B Mills, Peter T Clayton, Manuel Schiff

{"title":"Should PNPO Deficiency Be Treated In Utero? Clinical Findings From Prenatal Pyridoxine Therapy.","authors":"Chloé de Puyraimond, Samia Pichard, Muriel Girard, Julian Delanne, Laurence Faivre, Apolline Imbard, Amandine Baurand, Jean-François Benoist, Philippa B Mills, Peter T Clayton, Manuel Schiff","doi":"10.1002/jmd2.70086","DOIUrl":"10.1002/jmd2.70086","url":null,"abstract":"Pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency is characterized by early-onset epileptic encephalopathy refractory to standard antiseizure medications. It is caused by variants in the PNPO gene, resulting in deficient PNPO enzyme activity, which normally converts pyridoxine-5'-phosphate and pyridoxamine-5'-phosphate (two vitamers of vitamin B6) into the active cofactor, pyridoxal-5'-phosphate (PLP). Treatment relies on PLP or pyridoxine in some cases. Long-term outcomes remain suboptimal. We describe two cases of unrelated children treated with vitamin B6 (pyridoxine) in utero: one with a confirmed prenatal PNPO diagnosis and one at risk due to family history but ultimately unaffected. In utero pyridoxine, combined with early postnatal PLP treatment, allowed excellent seizure control and normal neurodevelopment in the long term. Notably, our first patient, treated from birth, is now 10 years old, representing the oldest reported PNPO-deficient individual treated from birth. Case 2 highlights the safety of prenatal B6 supplementation even in unaffected fetuses. These observations support prenatal pyridoxine supplementation as a safe and potentially beneficial strategy in at-risk PNPO pregnancies.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 3","pages":"e70086"},"PeriodicalIF":1.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1.8

JIMD reports Pub Date : 2026-04-20

引用次数: 0

IF 1.8

JIMD reports Pub Date : 2026-04-20

引用次数: 0

IF 1.8

JIMD reports Pub Date : 2026-04-13

引用次数: 0

Teriparatide in Two Patients With Mucopolysaccharidosis Type IVB. 特立帕肽治疗IVB型粘多糖病2例。

IF 1.8

JIMD reports Pub Date : 2026-04-13 eCollection Date: 2026-05-01 DOI: 10.1002/jmd2.70088

Mark Wijnen, Evert F S van Velsen, J Gert-Jan Milhous, Esmee Oussoren, Bram C J van der Eerden, Margreet A E M Wagenmakers

{"title":"Teriparatide in Two Patients With Mucopolysaccharidosis Type IVB.","authors":"Mark Wijnen, Evert F S van Velsen, J Gert-Jan Milhous, Esmee Oussoren, Bram C J van der Eerden, Margreet A E M Wagenmakers","doi":"10.1002/jmd2.70088","DOIUrl":"10.1002/jmd2.70088","url":null,"abstract":"Mucopolysaccharidosis Type IV is a multisystem lysosomal storage disease characterized by severe skeletal dysplasia resulting from impaired degradation of the glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. The condition is classified into Types A and B based on the underlying enzyme deficiency. Low bone mineral density (BMD) is a feature of the skeletal phenotype, contributing to increased fracture risk. Extraskeletal manifestations include, among others, cardiovascular disease due to valvular stenosis and regurgitation, myocardial remodeling, coronary artery disease, and vascular stiffness, all associated with glycosaminoglycan accumulation. We report two adult patients with mucopolysaccharidosis Type IVB treated with the osteoanabolic agent teriparatide for an apparently low BMD. The first patient presented with a non-healing femoral fracture requiring BMD improvement prior to surgical fixation. This patient was treated with teriparatide for 2 years, which resulted in significant BMD gain, enabling successful surgical fixation. The second patient received teriparatide for only 6 months and showed stable BMD. Notably, both patients developed serious cardiac problems during teriparatide treatment: the first patient experienced rapidly progressive aortic stenosis, while the second patient developed dyspnea and polyuria due to worsening dynamic left ventricular outflow tract obstruction, which had previously been asymptomatic. Both patients required invasive cardiac interventions, which carry high risk in mucopolysaccharidosis due to unique anatomical and anesthetic challenges. The temporal association between teriparatide treatment and the onset of cardiac problems in both patients is noteworthy and raises the possibility of a treatment-related effect. Therefore, we recommend cautious use of teriparatide in patients with mucopolysaccharidosis Type IV.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 3","pages":"e70088"},"PeriodicalIF":1.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0