更新于：2024-05-01
Carbamoyl-Phosphate Synthase I Deficiency Disease
氨基甲酰磷酸合酶I缺乏症
更新于：2024-05-01
基本信息
别名 CAPS deficiency、CARBAMOYL PHOSPHATE SYNTHETASE I DEFICIENCY、CARBAMOYL PHOSPHATE SYNTHETASE I DEFICIENCY, HYPERAMMONEMIA DUE TO + [66] |
简介 A urea cycle disorder manifesting in infancy as lethargy, emesis, seizures, alterations of muscle tone, abnormal eye movements, and an elevation of serum ammonia. The disorder is caused by a reduction in the activity of hepatic mitochondrial CARBAMOYL-PHOSPHATE SYNTHASE (AMMONIA). (Menkes, Textbook of Child Neurology, 5th ed, pp50-1) |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
Introduction of Tandem Mass Spectrometry (MS/MS) Technology in the Program of Selective Screening of Hereditary Metabolic Diseases in Kazakhstan
Universal Genomic Newborn Screening in the Wallonia-Brussels Federation: Baby Detect
Hepatic Histopathology in Urea Cycle Disorders
100 项与 氨基甲酰磷酸合酶I缺乏症 相关的临床结果
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100 项与 氨基甲酰磷酸合酶I缺乏症 相关的转化医学
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2023-11-30Modern rheumatology case reports
A case of cryopyrin-associated periodic syndrome due to somatic mosaic mutation complicated with recurrent circinate erythematous psoriasis.
Article
作者: Taiki Ando ; Yoshiyuki Abe ; Ken Yamaji ; Ryuta Nishikomori ; Naoto Tamura
Cryopyrin-associated periotic syndrome (CAPS) is a rare autoinflammatory disease (AID) caused by genetic variants in innate immunity genes. AIDs, including CAPS, mediate proinflammatory cytokines such as interleukin (IL)-1 and IL-18 and result in severe systemic inflammation. A gain-of-function mutation in the NLRP3 gene, which encodes the protein cryopyrin, was identified to be responsible for CAPS in 2001, and since then several additional pathogenic mutations have been found. Moreover, other phenotypes have been identified based on severity and symptomatology, including familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID)/chronic neurologic cutaneous articular syndrome (CINCA). Prompt diagnosis of CAPS remains challenging, however, due to unspecific, extensive clinical signs, and delayed diagnosis and treatment targeting IL-1 lead to multiorgan damage. Another factor complicating diagnosis is the existence of somatic mosaic mutations in the NLRP3 gene in some cases, resulting in symptoms and clinical courses that are atypical. The frequency of somatic mosaic mutations in CAPS was estimated to be 19% in a systematic review. Psoriasis is a chronic inflammatory skin disease that affects about 3% of the global population. Although no reports have shown complication between CAPS and psoriasis, these diseases have several similarities and potential relationships, for instance activation of Th17 cells in the dermis and increased NLRP3 gene expression in psoriatic skin compared with normal skin. Here we report a case of CAPS due to a somatic mosaic mutation with recurrent circinate erythematous psoriasis.
2023-11-14Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences
Long-term follow-up of children with carbamoyl phosphate synthase 1 deficiency detectedin newborn screening.
Article
作者: Zhanming Zhang ; Fan Tong ; Chi Chen ; Ting Zhang ; Guling Qian ; Xin Yang ; Xinwen Huang ; Rulai Yang ; Zhengyan Zhao
OBJECTIVES:
To investigate the incidence, genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province.
METHODS:
The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmedby tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed.
RESULTS:
A total of 4 056 755 newborns were screened during September 2013 to August 2023 in Zhejiang province, and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different mutations ofCPS1 genewere identified in genetic testing, including 2 known pathogenic mutations (c.2359C>T, c.1549+1G>T) and 8 unreported mutations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All affected infants had decreased citrulline levels (2.72-6.21 μmol/L),and varying degrees of elevated blood ammonia. Following diagnosis, the patients received restricted natural protein intake (special formula), ammonia scavenger and supportive therapy. They were followed up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and 1 patient each had attention deficit hyperactivity disorder (ADHD),transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages &Stages Questionnaires (ASQ) and GriffithsDevelopment Scales up to the present time; 4 cases had combined height or weight lag and 1 case was normal in height and weight.
CONCLUSIONS:
The estimated incidence of CPS1deficiency in Zhejiang province is approximately 1 in 680000. The common biochemical changes include low citrulline levels and hyperammonemia. Most mutations identified were specific to individual families, and no hotspot mutations have been found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of patients.
2023-06-26BMC medical genomics
Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review.
Review
作者: Shangyu Wang ; Jinglin Chen ; Xiaoqi Zhu ; Tingting Huang ; Haifeng Xu ; Guohuan Ying ; Hao Qian ; Wenxin Lin ; Yiehen Tung ; Kaleem Ullah Khan ; Hu Guo ; Guo Zheng ; Haiying Lu ; Gang Zhang
BACKGROUND:
Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1.
CASE PRESENTATION:
We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis.
CONCLUSION:
A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.
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