Hereditary cholestasis in childhood and infancy with normal serum gamma‐glutamyltransferase (GGT) activity is linked to several genes. Many patients, however, remain genetically undiagnosed. Defects in myosin VB (MYO5B; encoded by MYO5B) cause microvillus inclusion disease (MVID; MIM251850) with recurrent watery diarrhea. Cholestasis, reported as an atypical presentation in MVID, has been considered a side effect of parenteral alimentation. Here, however, we report on 10 patients who experienced cholestasis associated with biallelic, or suspected biallelic, mutations in MYO5B and who had neither recurrent diarrhea nor received parenteral alimentation. Seven of them are from two study cohorts, together comprising 31 undiagnosed low‐GGT cholestasis patients; 3 are sporadic. Cholestasis in 2 patients was progressive, in 3 recurrent, in 2 transient, and in 3 uncategorized because of insufficient follow‐up. Liver biopsy specimens revealed giant‐cell change of hepatocytes and intralobular cholestasis with abnormal distribution of bile salt export pump (BSEP) at canaliculi, as well as coarse granular dislocation of MYO5B. Mass spectrometry of plasma demonstrated increased total bile acids, primary bile acids, and conjugated bile acids, with decreased free bile acids, similar to changes in BSEP‐deficient patients. Literature review revealed that patients with biallelic mutations predicted to eliminate MYO5B expression were more frequent in typical MVID than in isolated‐cholestasis patients (11 of 38 vs. 0 of 13). Conclusion: MYO5B deficiency may underlie 20% of previously undiagnosed low‐GGT cholestasis. MYO5B deficiency appears to impair targeting of BSEP to the canalicular membrane with hampered bile acid excretion, resulting in a spectrum of cholestasis without diarrhea. (Hepatology 2017;65:1655‐1669).

Background and AimsLarge indels are commonly identified in patients but are not detectable by routine Sanger sequencing and panel sequencing. We specially designed a multi-gene panel that could simultaneously test known large indels in addition to ordinary variants, and reported the diagnostic yield in patients with intrahepatic cholestasis.MethodsThe panel contains 61 genes associated with cholestasis and 25 known recurrent large indels. The amplicon library was sequenced on Ion PGM system. Sequencing data were analyzed using a routine data analysis protocol and an internal program encoded for large indels test simultaneously. The validation phase was performed using 54 patients with known genetic diagnosis, including 5 with large insertions. At implement phase, 141 patients with intrahepatic cholestasis were evaluated.ResultsAt validation phase, 99.6% of the variations identified by Sanger sequencing could be detected by panel sequencing. Following the routine protocol, 99.8% of false positives could be filtered and 98.8% of retained variations were true positives. Large insertions in the 5 patients with known genetic diagnosis could be correctly detected using the internal program. At implementation phase, 96.9% of the retained variations, following the routine protocol, were confirmed to be true. Twenty-nine patients received a potential genetic diagnosis when panel sequencing data were analyzed using the routine protocol. Two additional patients, who were found to harbor large insertions in SLC25A13, obtained a potential genetic diagnosis when sequencing data were further analyzed using the internal program. A total of 31 (22.0%) patients obtained a potential genetic diagnosis. Nine different genetic disorders were diagnosed, and citrin deficiency was the commonest.ConclusionSpecially designed multi-gene panel can correctly detect large indels simultaneously. By using it, we assigned a potential genetic diagnosis to 22.0% of patients with intrahepatic cholestasis.

Background Long waiting times result in low satisfaction. Although several methods are used to shorten the actual waiting time (AWT) in large hospitals of China, the outpatients still have a long actual waiting time. This study aimed to explore whether satisfaction could be improved by extending the expected waiting time (EWT) instead of shortening the AWT. Methods In October 2016, 257 students in grade one voluntarily participated in this study. They came from 6 classes, which were randomly divided into two groups: 3 classes comprised the control group ( n = 125) and 3 classes comprised the experimental group ( n = 132). Unfavorable information (UI) was given to the experimental group alone. Six distinct questionnaires were designed to explore the effects of UI on EWT and the effects of an extended EWT on satisfaction. Satisfaction scores ranged from 0 to 100: 0–25, very dissatisfied; 26–50, dissatisfied; 51–75, satisfied; 76–100, very satisfied. Each participant finished one of the 6 questionnaires online. Of the 257 questionnaires, 233 were valid. Results Before UI was given, the initial EWT (T 0 ) was similar between the control and experimental groups ( Z = -1.924, P = 0.054). Under the effects of UI, individuals in the experimental group extended their EWT (T 1 ) from 121.0 to 180.0 min ( Z = -6.367, P < 0.001). Females prolonged their EWT longer than males did ( Z = -2.239, P = 0.025). Then, this study defined T 0 = 1.5 h and T 1 = 2.5 h, and compared the satisfaction scores between the control and experimental groups: a significant difference was found when AWT =2.0 h ( t = − 3.568, P = 0.001), but not when AWT =3.0 h ( t = − 0.718, P = 0.475) or when AWT =1.0 h ( t = − 1.088, P = 0.280). When AWT =3.0 h, fewer individuals felt “very dissatisfied” in the experimental group (21.2%) than in the control group (44.7%) ( χ 2 = 4.368, P = 0.037). Conclusions EWT was found to be extended greatly by UI. An extended EWT could improve satisfaction scores. Electronic supplementary material The online version of this article (10.1186/s12913-019-4408-3) contains supplementary material, which is available to authorized users.

CTX manifest as neonatal cholestasis has a bile acid profile different from CTX manifest in later life, and thus may be overlooked. Immunostaining, mass spectrometry of urine, and genetic studies can support one another in making the diagnosis. A substantial proportion of CTX patients with severe neonatal cholestasis may die or need liver transplantation. CTX manifest in infancy as severe cholestasis warrants further investigation of biochemical diagnostic criteria and best management.

Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7B gene detected two heterozygous disease causing mutations (c.2621C>T/p.A874V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.