Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes
Abstract Background Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder with heterogeneous clinical manifestations. This study aimed to characterize the clinical, biochemical, and genetic spectrum of NICCD and evaluate treatment outcomes. Methods...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12876-025-04008-5 |
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| author | Yigui Zou Yu Dai Liang Liu Qinghua Yang Wenwen Li Yilin Dong Sicong Li Yongwei Cheng Dongling Dai |
| author_facet | Yigui Zou Yu Dai Liang Liu Qinghua Yang Wenwen Li Yilin Dong Sicong Li Yongwei Cheng Dongling Dai |
| author_sort | Yigui Zou |
| collection | DOAJ |
| description | Abstract Background Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder with heterogeneous clinical manifestations. This study aimed to characterize the clinical, biochemical, and genetic spectrum of NICCD and evaluate treatment outcomes. Methods This retrospective cohort study analyzed molecularly confirmed cases of NICCD admitted to Shenzhen Children’s Hospital between March 2019 and April 2023. Comprehensive clinical data were extracted from electronic records and analyzed using descriptive statistical methods. Results The cohort (n = 15) demonstrated universal jaundice (100%) and hyperammonemia (93.3%), with the predominant c.851_854del variant (52%) associated with earliest onset (median 3 days) and most severe cholestatic features (100% jaundice, 60% hepatomegaly). Key metabolic abnormalities included universal citrulline elevation (100%) and frequent methionine increase (93.3%), while threonine/tyrosine disturbances showed genotype-dependent patterns. All patients achieved complete symptom resolution (median 32 days) and significant growth improvement with lactose-free MCT formula and ursodeoxycholic acid therapy, though rare variants (compound heterozygous c.1399 C > T/c.1638_1660dup) exhibited markedly prolonged recovery (88 days vs. cohort median 32 days). Conclusions This study delineates the clinical-genetic spectrum of NICCD and confirms the efficacy of MCT-based therapy. Genotype-phenotype correlations suggest variant-specific disease severity, warranting multicenter validation for rare mutations. |
| format | Article |
| id | doaj-art-b5875a4a4e7e49f494c90f467718c2bd |
| institution | DOAJ |
| issn | 1471-230X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | BMC Gastroenterology |
| spelling | doaj-art-b5875a4a4e7e49f494c90f467718c2bd2025-08-20T03:05:25ZengBMCBMC Gastroenterology1471-230X2025-07-0125111210.1186/s12876-025-04008-5Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomesYigui Zou0Yu Dai1Liang Liu2Qinghua Yang3Wenwen Li4Yilin Dong5Sicong Li6Yongwei Cheng7Dongling Dai8International Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalChildren’s Healthcare and Mental Health Center, Shenzhen Children’s HospitalInternational Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalInternational Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalInternational Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalInternational Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalInternational Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalDepartment of Gastroenterology, Shenzhen Children’s HospitalInternational Medical Center, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s HospitalAbstract Background Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder with heterogeneous clinical manifestations. This study aimed to characterize the clinical, biochemical, and genetic spectrum of NICCD and evaluate treatment outcomes. Methods This retrospective cohort study analyzed molecularly confirmed cases of NICCD admitted to Shenzhen Children’s Hospital between March 2019 and April 2023. Comprehensive clinical data were extracted from electronic records and analyzed using descriptive statistical methods. Results The cohort (n = 15) demonstrated universal jaundice (100%) and hyperammonemia (93.3%), with the predominant c.851_854del variant (52%) associated with earliest onset (median 3 days) and most severe cholestatic features (100% jaundice, 60% hepatomegaly). Key metabolic abnormalities included universal citrulline elevation (100%) and frequent methionine increase (93.3%), while threonine/tyrosine disturbances showed genotype-dependent patterns. All patients achieved complete symptom resolution (median 32 days) and significant growth improvement with lactose-free MCT formula and ursodeoxycholic acid therapy, though rare variants (compound heterozygous c.1399 C > T/c.1638_1660dup) exhibited markedly prolonged recovery (88 days vs. cohort median 32 days). Conclusions This study delineates the clinical-genetic spectrum of NICCD and confirms the efficacy of MCT-based therapy. Genotype-phenotype correlations suggest variant-specific disease severity, warranting multicenter validation for rare mutations.https://doi.org/10.1186/s12876-025-04008-5Citrin deficiencyNICCDSLC25A13Metabolic cholestasisOutcomes |
| spellingShingle | Yigui Zou Yu Dai Liang Liu Qinghua Yang Wenwen Li Yilin Dong Sicong Li Yongwei Cheng Dongling Dai Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes BMC Gastroenterology Citrin deficiency NICCD SLC25A13 Metabolic cholestasis Outcomes |
| title | Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes |
| title_full | Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes |
| title_fullStr | Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes |
| title_full_unstemmed | Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes |
| title_short | Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical features, genetic characteristics, and treatment outcomes |
| title_sort | neonatal intrahepatic cholestasis caused by citrin deficiency clinical features genetic characteristics and treatment outcomes |
| topic | Citrin deficiency NICCD SLC25A13 Metabolic cholestasis Outcomes |
| url | https://doi.org/10.1186/s12876-025-04008-5 |
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