Low prevalence of argininosuccinate lyase deficiency among inherited urea cycle disorders in Korea

A simple enzyme-multiple auxotroph assay has been developed for the identification of newborn infants with several of the inherited metabolic defects in the Krebs cycle for the detoxification of ammonia and in the ornithine metabolic pathway. This mass screening test is used with dried filter paper blood specimens and can easily be added to existing multiple testing programs presently used in screening for phenylketonuria or congenital hypothyroidism. This assay can be used to detect patients with citrullinemia, argininosuccinic acid lyase deficiency, and argininemia. In addition to these urea cycle disorders, the several types of ornithinemia, which can result in gyrate atrophy of the retina or mental retardation, should be detectable with this assay. The strengths and weaknesses of this assay are discussed and a large-scale pilot screening trial is proposed.

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Beclin-1-mediated activation of autophagy improves proximal and distal urea cycle disorders

10.1101/2020.07.22.216382 ◽

2020 ◽

Author(s):

Leandro R. Soria ◽

Dany P. Perocheau ◽

Giulia De Sabbata ◽

Angela De Angelis ◽

Gemma Bruno ◽

...

Keyword(s):

Urea Cycle ◽

Beclin 1 ◽

High Morbidity ◽

Urea Cycle Disorders ◽

Argininosuccinate Lyase ◽

Hepatocellular Injury ◽

Glycogen Accumulation ◽

Otc Deficiency ◽

Cycle Disorders ◽

Protein Rich

ABSTRACTUrea cycle disorders (UCD) are inherited defects in clearance of waste nitrogen with high morbidity and mortality. Novel and more effective therapies for UCD are needed. Studies in mice with constitutive activation of autophagy unraveled Beclin-1 as druggable candidate for therapy of hyperammonemia. Next, we investigated efficacy of cell penetrating autophagy inducing Tat-Beclin-1 (TB-1) peptide for therapy of the two most common UCD, namely ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL) deficiencies. TB-1 reduced urinary orotic acid and hyperammonemia, and improved survival under protein-rich diet in spf-ash mice, a model of OTC deficiency (proximal UCD). In AslNeo/Neo mice, a model of ASL deficiency (distal UCD), TB-1 increased ureagenesis, reduced argininosuccinate, and improved survival. Moreover, it alleviated hepatocellular injury and decreased both cytoplasmic and nuclear glycogen accumulation in AslNeo/Neo mice. In conclusion, Beclin-1-dependent activation of autophagy improved biochemical and clinical phenotypes of proximal and distal defects of the urea cycle.

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Mutation analysis of urea cycle disorders

Journal of Pediatric Biochemistry ◽

10.1055/s-0036-1586459 ◽

2016 ◽

Vol 04 (01) ◽

pp. 033-043

Author(s):

Johannes Häberle ◽

Véronique Rüfenacht

Keyword(s):

Mutation Analysis ◽

Urea Cycle ◽

Urea Cycle Disorders ◽

Cycle Disorders

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Human medicines European public assessment report (EPAR): Ravicti, glycerol phenylbutyrate, Urea Cycle Disorders, Inborn, Date of authorisation: 26/11/2015, Revision: 10, Status: Authorised

Case Medical Research ◽

10.31525/cmr-41abf0 ◽

2019 ◽

Author(s):

Keyword(s):

Urea Cycle ◽

Urea Cycle Disorders ◽

Assessment Report ◽

European Public ◽

European Public Assessment Report ◽

Cycle Disorders

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Retrospective evaluation of 85 patients with urea cycle disorders: one center experience, three new mutations

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0413 ◽

2020 ◽

Vol 33 (6) ◽

pp. 721-728

Author(s):

Özlem Saritaş Nakip ◽

Yılmaz Yıldız ◽

Ayşegül Tokatlı

Keyword(s):

Mortality Rate ◽

Urea Cycle ◽

Laboratory Data ◽

Patient Characteristics ◽

Hereditary Diseases ◽

Urea Cycle Disorders ◽

Carbamoyl Phosphate ◽

Term Survival ◽

Genetic Features ◽

Cycle Disorders

AbstractObjectivesUrea cycle disorders (UCDs) are rare hereditary diseases. This study was conducted to help identify the characteristics of UCDs in Turkey.MethodsThe primary outcome was to determine patient characteristics. Investigating the relationships between the patient outcomes and ammonia levels were the secondary outcomes. Eighty five patients from 79 families, diagnosed with UCD at a single metabolic referral center between 1979 and 2017, were included. Clinical and laboratory data were retrieved retrospectively from hospital records.ResultsClassical citrullinemia was the most common type of UCD; citrin deficiency and carbamoyl phosphate synthase 1 deficiency (CPS1D) were the rarest. One thirty one hyperammonemic episodes were recorded. The peak ammonia levels were found to be significantly associated with polycythemia and hypocalcemia at presentation. The median peak ammonia values of the patients who died were higher than those of the survivors. The highest mortality rate was in the classical citrullinemia group. The mortality rate of the first hyperammonemic crisis was 28.6%, while it was 6.7% in subsequent episodes with an odds ratio of 4.28 (95% CI: 1.67–11.0) (p=0.001). Forty-four patients underwent genetic analysis and genetic variants were detected in 42 patients (95%). Three of the detected variants have not been previously reported.ConclusionsThis is the largest UCD series in Turkey and may serve as a guide to clinical, biochemical and genetic features of UCDs in our country. Prevention of hyperammonemia may be the most influential measure to improve long term survival.

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