Clinical and Molecular Characteristics of 69 Chinese Patients with Ornithine Transcarbamylase Deficiency

Abstract Background: This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype.Methods: Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records. Results: Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range, 1 day-56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P < 0.01). Fifty-four different mutations of OTC gene were identified and 18 of them were novel. R277W (10.6%) was the most common mutation, followed by G195R (4.6%) and A209V (3.0%). By June 2019, 41 patients had survived, 24 were deceased, and 4 were lost to follow-up. Among the survivors, 13 patients had received liver transplantation at a median age of 3 years, with a one-year survival rate of 100%. The mortality of OTCD is extremely high among patients with early onset (80.0% versus 24.5% in patients with late onset).Conclusions: The evaluation of serum citrulline level is of limited value in diagnosis of OTCD, while urine orotic acid detection and genetic testing are more helpful.

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Clinical and molecular characteristics of 69 Chinese patients with ornithine transcarbamylase deficiency

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01606-2 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Deyun Lu ◽

Feng Han ◽

Wenjuan Qiu ◽

Huiwen Zhang ◽

Jun Ye ◽

...

Keyword(s):

Early Onset ◽

Orotic Acid ◽

Late Onset ◽

Peak Plasma ◽

Laboratory Data ◽

Ornithine Transcarbamylase ◽

Chinese Patients ◽

Molecular Characteristics ◽

Common Mutation ◽

Ornithine Transcarbamylase Deficiency

Abstract Background This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype. Methods Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records. Results Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range 1 day–56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P < 0.01). Fifty-four different mutations of OTC gene were identified and 18 of them were novel. R277W (10.6%) was the most common mutation, followed by G195R (4.6%) and A209V (3.0%). By June 2019, 41 patients had survived, 24 were deceased, and 4 were lost to follow-up. Among the survivors, 13 patients had received liver transplantation at a median age of 3 years, with a one-year survival rate of 100%. The mortality of OTCD is extremely high among patients with early onset (80.0% versus 24.5% in patients with late onset). Conclusions The evaluation of serum citrulline level is of limited value in diagnosis of OTCD, while urine orotic acid detection and genetic testing are more helpful.

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1H MRS allows brain phenotype differentiation in sisters with late onset ornithine transcarbamylase deficiency (OTCD) and discordant clinical presentations

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2007.12.008 ◽

2008 ◽

Vol 94 (1) ◽

pp. 52-60 ◽

Cited By ~ 11

Author(s):

Andrea L. Gropman ◽

Rebecca R. Seltzer ◽

Marc Yudkoff ◽

Alice Sawyer ◽

John vanMeter ◽

...

Keyword(s):

Late Onset ◽

Ornithine Transcarbamylase ◽

Ornithine Transcarbamylase Deficiency ◽

1H Mrs ◽

Clinical Presentations

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Clinical and Neuroimaging Characterization of Chinese Dementia Patients with PSEN1 and PSEN2 Mutations

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000366272 ◽

2014 ◽

Vol 39 (1-2) ◽

pp. 32-40 ◽

Cited By ~ 18

Author(s):

Zhihong Shi ◽

Ying Wang ◽

Shuai Liu ◽

Mengyuan Liu ◽

Shuling Liu ◽

...

Keyword(s):

Early Onset ◽

Late Onset ◽

Novel Mutation ◽

Chinese Patients ◽

Phenotypic Traits ◽

Chinese Han ◽

Risk Variants ◽

Dementia Patients ◽

Positron Emission ◽

Neurodegenerative Dementia

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two common forms of primary neurodegenerative dementia. Mutations in 3 genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset AD. Methods: We performed gene sequencing in PSEN1, PSEN2, and APP in 61 AD and 35 FTD Chinese patients. Amyloid load using 11C-labeled Pittsburgh compound B (11C-PIB) positron emission tomography (PET) and cerebral glucose metabolism using 18F-fludeoxyglucose PET were evaluated in patients carrying mutations. Results: We identified 1 known pathogenic PSEN1 (p.His163Arg, c.488A>G) mutation and 3 novel PSEN2 mutations in 6 patients. The novel mutation PSEN2 (p.His169Asn, c.505C>A) was identified in 1 patient with familial late-onset AD and in 1 sporadic FTD patient. The PSEN2 (p.Val214Leu, c.640G>T; p.Lys82Arg, c.245A>G) mutations were identified in 2 early-onset AD patients and 1 early-onset AD patient, respectively. Three patients with PSEN2 mutations were observed to have PIB retention on the cortex and striatum. One patient with the FTD phenotype was not observed to have PIB retention. Conclusion: PSEN2 mutations are common in the Chinese Han population with a history of AD and FTD. Pathogenic mutations or risk variants in the PSEN2 gene can influence both FTD and AD phenotypic traits and show variations in neuroimaging characterization. © 2014 S. Karger AG, Basel

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Case 252: Acute Hyperammonemic Encephalopathy Resulting from Late-Onset Ornithine Transcarbamylase Deficiency

Radiology ◽

10.1148/radiol.2018161834 ◽

2018 ◽

Vol 287 (1) ◽

pp. 353-359

Author(s):

Michelle Hershman ◽

Raymond Carmody ◽

Unni K. Udayasankar

Keyword(s):

Late Onset ◽

Ornithine Transcarbamylase ◽

Ornithine Transcarbamylase Deficiency ◽

Hyperammonemic Encephalopathy

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Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-314281 ◽

2019 ◽

Vol 104 (7) ◽

pp. 932-937 ◽

Cited By ~ 3

Author(s):

Ke Xu ◽

Yue Xie ◽

Tengyang Sun ◽

Xiaohui Zhang ◽

Chunjie Chen ◽

...

Keyword(s):

Early Onset ◽

Retinal Dystrophy ◽

Case Series ◽

Clinical Findings ◽

Chinese Patients ◽

Pcr Analysis ◽

Common Mutation ◽

Essential Information ◽

Leber Congenital Amaurosis ◽

Targeted Next Generation Sequencing

BackgroundLeber congenital amaurosis (LCA) and early onset severe retinal dystrophy (EOSRD) are clinically and genetically heterogeneous inherited retinal disorders that cause severe visual impairment in children. The objective of this study was to describe the mutation profile and phenotypic characteristics in Chinese patients with LCA or EOSRD.MethodsRetrospective consecutive case series (2010–2017) study was performed in 148 probands (91 with LCA and 57 with EOSRD). All patients underwent ophthalmic evaluation. Mutations were revealed using targeted next-generation sequencing, followed by Sanger DNA-sequencing and real-time quantitative PCR analysis.ResultsWe identified two diseasing-causing mutations in 88 unrelated patients, heterozygous autosomal dominant mutations in 11 probands and X-linked hemizygous mutations in 11 patients, for an overall mutation detection rate of 74.3% (110/148). We detected 158 different disease-causing mutations involving 14 LCA genes, 16 retinitis pigmentosa or cone-rod dystrophy genes and 3 syndromic retinal dystrophy genes. Of these 158 mutations, 98 were novel. The most common mutation was p.Q141X of AIPL1, with a gene-specific allele frequency of 60%. The first five most frequently mutated genes were AIPL1 (11.0%), RPGRIP1 (8.8%) and CEP290, GUCY2D and RPE65 (each 7.7%) in the patients with LCA and RPGR (12.3%), CRB1 (10.5%), RPE65 (10.5%), RDH12 (7.0%) and RP2 (5.3%) in the patients with EOSRD.ConclusionsOur results revealed that the mutation spectrum of patients with LCA differs from that of the patients with EOSRD and established the configuration of the mutation frequencies for each LCA gene in Chinese patients, thereby providing essential information for future genetic counselling and gene therapy.

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Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20040968 ◽

2019 ◽

Vol 20 (4) ◽

pp. 968 ◽

Cited By ~ 6

Author(s):

Edurne Álvaro ◽

Juana M. Cano ◽

Juan L. García ◽

Lorena Brandáriz ◽

Susana Olmedillas-López ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Cpg Island ◽

Low Frequency ◽

Tumor Location ◽

Molecular Characteristics ◽

Braf Mutations ◽

Rectal Cancers

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.

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