Citrin deficiency: A treatable cause of acute psychosis in adults

Bijarnia‐Mahay, Sunita; Häberle, Johannes; Rüfenacht, Véronique; Shigematsu, Yosuke; Saxena, Renu; Verma, Ishwar C.

doi:10.4103/0028-3886.156285

Cited by 14 publications

(9 citation statements)

References 8 publications

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“…Rest of mutations were single nucleotide substitutions, missense or nonsense mutations. Pathogenic variants were also identified in arginase deficiency (5 cases), CPS1 deficiency (3 cases), two cases of NAGS deficiency, one case each citrin deficiency [ 10 ] and LPI [ 11 ]. All pathogenic variants in ARG1 and NAGS genes were novel (Tables 2 and 3 ).…”

Section: Resultsmentioning

confidence: 99%

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Bijarnia-Mahay

Häberle

Jalan

et al. 2018

Orphanet J Rare Dis

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BackgroundUrea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile.ResultsWe present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed.Molecular genetic analysis revealed two common ASS1 mutations: c.470G > A (p.Arg157His) and c.1168G > A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis.ConclusionsWe report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0908-1) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Bijarnia-Mahay

Häberle

Jalan

et al. 2018

Orphanet J Rare Dis

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“…Although about 200 Chinese NICCD patients have been diagnosed via SLC25A13 analysis to date 22 25 26 27 , this number was rather limited, since China might have 85700 CD patients according to provisional epidemiological data 19 27 28 . Moreover, the SLC25A13 mutations worldwide demonstrate remarkable heterogeneity 12 22 23 24 27 29 30 31 32 33 34 35 36 37 38 . China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients, including the mutation spectrum and their geographic distribution, remains far from being well clarified in our country.…”

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confidence: 99%

Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution

Lin

Zeng

Zhang

et al. 2016

Sci Rep

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Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A > G, [c.329 − 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C > T, c.755 − 1G > C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G > T, c.1452 + 1G > A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C > T, c.851_854del4, c.1078C > T, IVS11 + 1G > A, c.1364G > T, c.1399C > T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C > T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas.

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“…Nevertheless, as of today, there are no well-recognized clinical and biochemical criteria for NICCD diagnosis, and SLC25A13 gene and/or its expression product analysis has been taken as the reliable diagnostic tools. To date, a total of 106 pathogenic SLC25A13 mutations/variations have been reported [ 11 , 14 , 22 , 25 , 32 – 41 ], most of which are point mutations or short insertions/deletions. Among the SLC25A13 mutations detected in Chinese CD patients, c.851_854del, c.1638_1660dup, c.615+5G>A and IVS16ins3kb account for about 85% of all mutated alleles [ 11 , 25 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular diagnosis of citrin deficiency in an infant with intrahepatic cholestasis: identification of a 21.7kb gross deletion that completely silences the transcriptional and translational expression of the affected SLC25A13 allele

et al. 2017

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Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) arises from biallelic SLC25A13 mutations, and SLC25A13 analysis provides reliable evidences for NICCD definite diagnosis. However, novel large insertions/deletions in this gene could not be detected just by conventional DNA analysis. This study aimed to explore definite diagnostic evidences for an infant highly-suspected to have NICCD. Prevalent mutation screening and Sanger sequencing of SLC25A13 gene just revealed a paternally-inherited mutation c.851_854del4. Nevertheless, neither citrin protein nor SLC25A13 transcripts of maternal origin could be detected on Western blotting and cDNA cloning analysis, respectively. On this basis, the hidden maternal mutation was precisely positioned using SNP analysis and semi-quantitative PCR, and finally identified as a novel large deletion c.-3251_c.15+18443del21709bp, which involved the SLC25A13 promoter region and the entire exon 1 where locates the translation initiation codon. Hence, NICCD was definitely diagnosed in the infant. To the best of our knowledge, the novel gross deletion, which silenced the transcriptional and translational expression of the affected SLC25A13 allele, is the hitherto largest deletion in SLC25A13 mutation spectrum. The Western blotting approach using mitochondrial protein extracted from expanded peripheral blood lymphocytes, of particular note, might be a new minimally-invasive and more-feasible molecular tool for NICCD diagnosis.

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Citrin deficiency: A treatable cause of acute psychosis in adults

Cited by 14 publications

References 8 publications

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution

Molecular diagnosis of citrin deficiency in an infant with intrahepatic cholestasis: identification of a 21.7kb gross deletion that completely silences the transcriptional and translational expression of the affected SLC25A13 allele

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