Liver transplantation in a boy with TFAM mutation associated mtDNA depletion syndrome.

Mitochondrial transcription factor A (TFAM) deficiency may cause mtDNA depletion syndrome, which manifests as neonatal liver failure or primary ovarian insufficiency, hearing loss, seizures, and intellectual disability. Treatment focusing on symptomatic management, and the clinical prognosis remains poor. Here, we describe a novel case of TFAM mutation presenting with progressive neonatal cholestasis, hypoglycemia and abnormal amino acid profiling.

Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study.

Background: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients.

Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study.

Objective: To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA).

Methods: This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR.

NR1H4 disease: rapidly progressing neonatal intrahepatic cholestasis and early death.

Background: Clinical studies on progressive familial intrahepatic cholestasis (PFIC) type 5 caused by mutations in NR1H4 are limited.

Methods: New patients with biallelic NR1H4 variants from our center and all patients from literature were retrospectively analyzed.

Results: Three new patients were identified to be carrying five new variants.

Non-invasive biomarkers for identification of vanishing bile duct syndrome among children with acute cholestatic hepatitis.

Background: The identification of vanishing bile duct syndrome (VBDS) is still challenging before liver biopsy. This study tried to explore non-invasive biomarkers for identification of VBDS among children with acute cholestatic hepatitis.

Methods: Between January 2017 and December 2021, 192 children underwent native-liver biopsy for acute cholestatic hepatitis with onset after 6 months of age.

Neonatal cholestasis as the onset symptom of McCune-Albright syndrome: case reports and a literature review.

Aim: This study aimed to summarize and show the characteristics and evolutionary process of neonatal cholestasis caused by McCune-Albright syndrome (MAS), as neonatal cholestasis may be the initial manifestation of MAS before other classic clinical features appear.

Methods: The clinical characteristics, treatment methods, and outcomes of three neonatal cholestasis cases caused by MAS in our center were retrospectively studied. In addition, all the reported cases of MAS combined with cholestasis were reviewed and summarized to show the cholestatic features in them.

[A rare case of neonatal-onset hepatic sinusoidal obstruction syndrome].

A male infant, aged 1 month and 14 days, was admitted to the hospital due to abdominal distension lasting for 2 weeks and worsening for 3 days. The infant had a history of omphalitis. Physical examination revealed severe abdominal distension, prominent abdominal wall veins, hepatosplenomegaly, and massive ascites.

Recurrent AKR1D1 c.580-13T>A Variant: A Cause of Δ-3-Oxosteroid-5β-Reductase Deficiency.

Δ-3-oxosteroid 5β-reductase (AKR1D1) deficiency presents with neonatal cholestasis and liver failure in early infancy and features high levels of 3-oxo-Δ-bile acids in urine. Genetic analysis is needed for definitive diagnosis, because in the neonatal period it can be difficult to distinguish a primary from a secondary enzyme deficiency. By re-analysis of the gene-sequencing data, one AKR1D1 noncanonical splice-site variant (NM_005989.

Poly-hydroxylated bile acids and their prognostic roles in Alagille syndrome.

Background: The liver manifestations of Alagille syndrome (ALGS) are highly variable, and factors affecting its prognosis are poorly understood. We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.

Methods: Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.

Defining pathogenicity of NOTCH2 variants for diagnosis of Alagille syndrome type 2 using a large cohort of patients.

Background And Aims: Alagille syndrome (ALGS) type 2 caused by mutations in NOTCH2 has genotypic and phenotypic heterogeneity. Diagnosis in some atypical patients with isolated hepatic presentation could be missed.

Methods: Using 2087 patients with paediatric liver manifestations, NOTCH2 allele frequencies, in-silico prediction, protein domains and clinical features were analysed to define the pathogenicity of NOTCH2 variants for diagnosis of ALGS type 2.

Neonatal cholestasis is an early liver manifestation of children with acid sphingomyelinase deficiency.

Background: Patients with acid sphingomyelinase deficiency (ASMD) may be referred to a hepatologist for liver manifestations. This study summarized the liver manifestations of patients with ASMD in the early disease course.

Methods: This study enrolled ASMD patients diagnosed by genetic tests between July 2016 and December 2020 in a national pediatric liver center.

The Presence of Vacuolated Kupffer Cells Raises a Clinical Suspicion of Niemann-Pick Disease Type C in Neonatal Cholestasis.

Early diagnosis of Niemann-Pick disease type C (NP-C) in neonatal cholestasis is still challenging because splenomegaly is non-specific and oxysterol profiling studies also have a relatively low specificity. This study explores a method for identifying infants with a high clinical suspicion of NP-C in neonatal cholestasis. We reviewed the clinical findings of 9 neonatal cholestatic infants with NP-C genetically diagnosed between January 2015 and December 2020.

Comparison of Two Donor Liver Procurement Methods for Treatment of Pediatric Acute Liver Failure.

Background: To evaluate the difference and efficacy of two donor liver procurement methods for treatment of pediatric acute liver failure (PALF) by living donor liver transplantation (LDLT).

Methods: A total of 17 patients (12 men, 5 women) with PALF who underwent LDLT in our hospital between October 2016 and October 2020, and prognostic efficacy of donors and recipients using two donor liver procurement methods were analyzed.

Results: The donors and recipients were both divided into laparoscopic (7 cases) and open (10 cases) donor liver procurement groups.

Genetic spectrum and clinical characteristics of 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) deficiency in China.

Background: Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy.

Methods: The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder.

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices.

Background: Acute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable.

A Novel, Recurrent, 3.6-kb Deletion in the PYGL Gene Contributes to Glycogen Storage Disease Type VI.

The PYGL gene is the only established gene known to cause glycogen storage disease type VI (GSD6), which is a rare autosomal recessive disorder associated with hepatomegaly, elevated levels of hepatic transaminases, and hypoglycemia. Extended bioinformatics analysis was performed on the exome sequencing data of 5 patients who were clinically diagnosed as having or highly suspected of having GSD, and a single heterozygous pathogenic or likely pathogenic or rare variant of uncertain significance single-nucleotide variant was identified on the PYGL gene. A recurrent, novel, 3.

Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review.

Objectives The aim of our study is to systematically describe the genotypic and phenotypic spectrum of Glycogen storage disease type VI (GSD VI), especially in Chinses population.  Methods We retrospectively analyzed ten Chinese children diagnosed as having GSD VI confirmed by next generation sequencing in Children's Hospital of Fudan University and Jinshan Hospital of Fudan University. We described the genotypic and phenotypic spectrum of GSD VI through the clinical and genetic data we collected.

Feeding practices in 6-24-month-old children with chronic cholestatic liver diseases: a mixed-method study.

Background: Children with chronic cholestatic liver diseases have a high risk of malnutrition. However, nutritional management in China has received little attention, and there has been limited evidence regarding improving these practices. This study aimed to evaluate the feeding status of chronic cholestatic children aged 6-24 months and to explore their parents' experiences with feeding practices.

NBAS disease: 14 new patients, a recurrent mutation, and genotype-phenotype correlation among 24 Chinese patients.

Aim: Neuroblastoma amplified sequence (NBAS)-associated disease has a wide phenotypic spectrum, including infantile liver failure syndrome type 2 (ILFS2, OMIM #616483), short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome (OMIM #614800), and a combined phenotype overlapping ILFS2 and SOPH syndrome. The mutation spectra of NBAS and its genotype-phenotype correlation among Chinese were not clear.

Methods: Clinical and genetic data were retrospectively collected from the medical charts of patients with biallelic NBAS mutations, as well as from Chinese patients in previously published reports.

ABCB11 deficiency presenting as transient neonatal cholestasis: Correlation with genotypes and BSEP expression.

Background & Aims: ABCB11 deficiency presenting in infancy is believed generally to manifest as persistent/progressive cholestasis. We describe a group of patients with biallelic ABCB11 variants whose disorder manifested as transient neonatal cholestasis (TNC).

Methods: Neonatal intrahepatic cholestasis in 68 children (31 males) with biallelic predictedly pathogenic variants (PPV) in ABCB11 was classified as transient (TNC group, n = 23, 11 males), intermittent (benign recurrent intrahepatic cholestasis [BRIC] group, n = 3, 1 male) or persistent/ progressive (progressive familial intrahepatic cholestasis [PFIC] group, n = 42, 19 males).

Low-GGT intrahepatic cholestasis associated with biallelic USP53 variants: Clinical, histological and ultrastructural characterization.

Background & Aims: In about 20% of children with cholestasis and normal or low serum gamma-glutamyltransferase (GGT) activity, no aetiology is identified. We sought new genes implicated in paediatric hepatobiliary disease.

Methods: We conducted whole-exome sequencing in 69 children evaluated at our centre from 2011 to 2018 who had low-GGT cholestasis and in whom homozygous/compound heterozygous predictedly pathogenic variants (PPVs) in ATP8B1, ABCB11, NR1H4, MYO5B or TJP2 were not found.