Biallelic Mutations in Ubiquitin-Specific Peptidase 53 (USP53) Causing Progressive Intrahepatic Cholestasis. Report of a Case With Review of Literature

2021 ◽  
pp. 109352662110511
Author(s):  
Mukul Vij ◽  
Srinivas Sankaranarayanan
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Liver Biopsy ◽  
Intrahepatic Cholestasis ◽  
Cholestatic Liver Disease ◽  
Review Of Literature ◽  
Biallelic Mutation ◽  
Whole Exome ◽  
Sequencing Studies ◽  
Biallelic Mutations

Whole-exome sequencing studies have recently identified novel genes implicated in normal- or low-GGT pediatric cholestasis including ubiquitin-specific peptidase 53 ( USP53). We identified novel biallelic mutations in the USP53 gene in a 7-month-old infant with pruritus and progressive intrahepatic cholestasis. His liver biopsy showed portal and perivenular fibrosis with bland bilirubinostasis. His parents were asymptomatic heterozygous for the same mutation. He is currently on vitamin supplements and cholestyramine and his family has also been counseled for liver transplantation. Our report confirms that patients with biallelic mutation in USP53 develop cholestatic liver disease.

Expanding Clinical Phenotype of TRAPPC12-Related Childhood Encephalopathy: Two Cases and Review of Literature

2020 ◽  
Vol 51 (06) ◽  
pp. 430-434
Author(s):  
Ayca Dilruba Aslanger ◽  
Emine Demiral ◽  
Seyma Sonmez-Sahin ◽  
Serhat Guler ◽  
Beyza Goncu ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Cerebellar Atrophy ◽  
Cortical Atrophy ◽  
Review Of Literature ◽  
Neurodevelopmental Delay ◽  
Phenotypic Spectrum ◽  
Progressive Encephalopathy ◽  
Whole Exome ◽  
Biallelic Mutations ◽  
Generation Sequencing

AbstractBiallelic mutations in the TRAPPC12 gene are responsible for early-onset progressive encephalopathy with brain atrophy and spasticity (PEBAS). To date, three different allelic variants have been reported. Next-generation sequencing allowed discovery of unique alternations in this gene with different phenotypes. We report two patients carrying TRAPPC12 variants, one previously reported and one unknown mutation, with severe neurodevelopmental delay and brain atrophy. Standard clinical examination and cranial imaging studies were performed in these two unrelated patients. In addition, whole-exome sequencing was performed, followed by Sanger sequencing for verification. The first patient, a 2-year-old boy, was found to be homozygous for the previously reported c.1880C > T (p.Ala627Val) mutation. He presented with a phenotype including severe progressive cortical atrophy, moderate cerebellar atrophy, epilepsy, and microcephaly, very similar to the previously reported cases. The second case, a 9-year-old boy, carried a novel homozygous c.679T > G (p.Phe227Val) variant and presented with mild cortical atrophy, severe cerebellar atrophy, and neither clinically manifest epilepsy nor microcephaly, which were previously considered typical findings in PEBAS with TRAPPC12 mutations. Our findings suggest that clinical and brain imaging findings might be more variable than previously anticipated; however, a larger number of observations would benefit for broader phenotypic spectrum.

Quality of life before and after liver transplantation for cholestatic liver disease

Hepatology ◽  
1999 ◽  
Vol 29 (2) ◽  
pp. 356-364 ◽  
Author(s):  
Cynthia R. Gross ◽  
Michael Malinchoc ◽  
W. Ray Kim ◽  
Roger W. Evans ◽  
Russell H. Wiesner ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Cholestatic Liver Disease ◽  
Before And After

scholarly journals The Role of Liver Biopsy in Investigation of Cholestatic Liver Disease in Infancy

2018 ◽  
Vol 2 (2) ◽  
pp. 51-56
Author(s):  
Zoya Chaudhry ◽  
Sylviane Forget ◽  
Van-Hung Nguyen ◽  
Najma Ahmed
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Cholestatic Liver Disease

Bone Histomorphometric Changes After Liver Transplantation for Chronic Cholestatic Liver Disease

2003 ◽  
Vol 18 (12) ◽  
pp. 2190-2199 ◽  
Author(s):  
Maureen MJ Guichelaar ◽  
Michael Malinchoc ◽  
Jean D Sibonga ◽  
Bart L Clarke ◽  
J Eileen Hay
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Cholestatic Liver Disease

scholarly journals Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mariam Goubran ◽  
Ayodeji Aderibigbe ◽  
Emmanuel Jacquemin ◽  
Catherine Guettier ◽  
Safwat Girgis ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Intrahepatic Cholestasis ◽  
Autoimmune Response ◽  
Compound Heterozygous ◽  
Biliary Cirrhosis ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Type 3

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. Case presentation We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient’s original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. Conclusions Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

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