Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin, typically seen in infancy or childhood caused by a defect in the ABCB4 located on chromosome 7. Here we report on an older patient, aged 15, who presented with biochemical testing that led to an initial consideration of a diagnosis of Wilson disease (WD) resulting in a delayed diagnosis of PFIC3. Diagnosis of PFIC3 was later confirmed by molecular studies that identified novel mutations in the ABCB4 gene. Cholestasis due to PFIC3 can cause elevated hepatic copper and increased urine copper excretion that overlap with current diagnostic criteria for WD. Molecular diagnostics are very useful for establishing the diagnosis of PFIC3. Ursodeoxycholic acid ameliorates cholestasis in PFIC3, and may help mediate a reduction in hepatic copper content in response to treatment.
Cholestasis ; Cholestasis, Intrahepatic* ; Chromosomes, Human, Pair 7 ; Copper ; Delayed Diagnosis ; Diagnosis* ; Hepatolenticular Degeneration* ; Humans ; Molecular Biology* ; Pathology, Molecular ; Ursodeoxycholic Acid

Hypertrophic olivary degeneration resulting from lesions of the dento-rubro-olivary pathway, also called Guillain-Mollaret-triangle, has been described previously in a number of cases. Reports about bilateral hypertrophic olivary degeneration of the inferior olivary nuclei are very limited, and the magnetic resonance imaging findings of hypertrophic olivary degeneration in Wilson disease have not yet been described to the best of our knowledge. Herein, we present the first report of bilateral hypertrophic olivary degeneration diagnosed by magnetic resonance imaging in a patient suffering from Wilson disease.
Diagnosis, Differential ; Hepatolenticular Degeneration/*pathology ; Humans ; Hypertrophy/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Nerve Degeneration/*pathology ; Olivary Nucleus/*pathology ; Young Adult

Adenosine Triphosphatases ; genetics ; Alanine Transaminase ; blood ; Cation Transport Proteins ; genetics ; Ceruloplasmin ; metabolism ; Child ; Copper ; blood ; urine ; Copper-transporting ATPases ; Cornea ; pathology ; Diagnosis, Differential ; Genetic Testing ; Hepatolenticular Degeneration ; blood ; diagnosis ; genetics ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Function Tests ; Mutation

OBJECTIVETo reassess the diagnostic value of 24 hour urinary copper excretion in children with Wilson disease (WD).

METHODSFrom July 2005 to June 2007, inpatients over three years old in a pediatric liver center were assigned into WD and non-WD group.

RESULTS94 patients, including 26 cases in WD and 68 in non-WD group, were enrolled in this study. The median of 24 h urinary copper excretion was 98.5 microg in WD group and 25.8 microg in the non-WD group (Z = -6.111, P equal to 0.000). The area under receiver operator curve (ROC) was 0.909 (95% CI: 0.839-0.979, P equal to 0.000). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6% and 93.9% respectively using 52.0 ug as a cutoff value, and 50.0%, 97.1%, 84.0%, 86.7% and 83.5% using 100 microg as a cutoff value. The goodness of fitness of 52 microg criteria was significantly higher than 100 microg criteria (kappacoefficient 0.760, 0.541 respectively, P equal to 0.000).

CONCLUSIONComparing to 100, 52 microg of 24 h urinary copper excretion as a cutoff value significantly improves the sensitivity and accuracy for diagnosing WD in children.

Adolescent ; Age Factors ; Ceruloplasmin ; Child ; Child, Preschool ; Copper ; urine ; Female ; Hepatitis ; diagnosis ; pathology ; urine ; Hepatitis A ; diagnosis ; pathology ; urine ; Hepatolenticular Degeneration ; diagnosis ; pathology ; urine ; Humans ; Liver ; pathology ; Male ; Penicillamine ; Predictive Value of Tests ; ROC Curve ; Sensitivity and Specificity ; Time Factors

OBJECTIVE: To determine whether there is a correlation between liver MR findings and the clinical manifestations and severity of liver dysfunction in patients with Wilson's disease. MATERIALS AND METHODS: Two radiologists retrospectively evaluated MR images of the liver in 50 patients with Wilson's disease. The Institutional Review Board approved this retrospective study and informed consent was waived. MR images were evaluated with a focus on hepatic contour abnormalities and the presence of intrahepatic nodules. By using Fisher's exact test, MR findings were compared with clinical presentations (neurological and non-neurological) and hepatic dysfunction, which was categorized by the Child-Pugh classification system (A, B and C). Follow-up MR images were available for 17 patients. RESULTS: Contour abnormalities of the liver and intrahepatic nodules were observed in 31 patients (62%) and 25 patients (50%), respectively. Each MR finding showed a statistically significant difference (p < 0.05) among the three groups of Child-Pugh classifications (A, n = 36; B, n = 5; C, n = 9), except for splenomegaly (p = 0.243). The mean age of the patients with positive MR findings was higher than that of patients with negative MR findings. For patients with Child-Pugh class A (n = 36) with neurological presentation, intrahepatic nodules, surface nodularity, and gallbladder fossa widening were more common. Intrahepatic nodules were improved (n = 8, 47%), stationary (n = 5, 29%), or aggravated (n = 4, 24%) on follow-up MR images. CONCLUSION: MR imaging demonstrates the contour abnormalities and parenchymal nodules of the liver in more than half of the patients with Wilson's disease, which correlates with the severity of hepatic dysfunction and clinical manifestations.
Adolescent ; Adult ; Chi-Square Distribution ; Child ; Child, Preschool ; Female ; Hepatolenticular Degeneration/*diagnosis/pathology ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Male ; Retrospective Studies ; Statistics, Nonparametric

OBJECTIVETo review the clinical features and liver pathology in children with hepatolenticular degeneration.

METHODSClinical manifestations and results of lab tests and liver biopsies of 97 cases diagnosed as hepatolenticular degeneration in Children's Hospital of Fudan University from Jan 1990 to Nov 2006 were reviewed.

RESULTSManifestations of liver malfunction were the most common reason (74%) for their clinic visits. All cases showed liver involvement and nervous system involvement was found in 45%. Positive K-F rings were detected in 63 of 95 cases; ceruloplasmin level was low in 91 of the 94 cases, and 24 hour urinary copper excretion exceeded 100 microg in 25 out of 37 cases who had had this test. Seventeen cases had a liver biopsy. Various levels of inflammation and fibrosis were noted in all 17 biopsies; 8 of the 17 also had steatosis and 3 of the 17 also had glycogen accumulation.

CONCLUSIONLiver abnormality is a consistent feature in children with hepatolenticular degeneration. Corneal K-F rings, serum ceruloplasmin and the 24-hour urinary copper test have limited values for an early diagnosis of the disease. Liver pathology can be a reference in the diagnosis of hepatolenticular degeneration.

Adolescent ; Child ; Child, Preschool ; Female ; Hepatolenticular Degeneration ; diagnosis ; pathology ; Humans ; Liver ; pathology ; Male ; Retrospective Studies

Adolescent ; Child ; Female ; Hepatolenticular Degeneration ; diagnosis ; genetics ; pathology ; Humans

OBJECTIVESTo study the feasibility and possibility to diagnose Wilson disease with electronmicroscopical examination of liver biopsies.

METHODSClinical analysis, histological observation and ultrastructural examination were performed on 15 children with Wilson disease.

RESULTSAll 15 subjects had symptoms of hepatic disorders, such as jaundice. Morphological signs of hepatocyte injury in three phase, namely steatosis, mitochondrion changes and cholestasis in bile canaliculi of the early phase, nucleus injury, dilation of endoplasmic reticulum, increase of lysosomes and appearance of residual bodies of the second phase, and massive autophagy and cirrhosis of the late phase were shown. A few inflammatory cells in the liver specimens were observed. Accumulation of copper in lysosomes and autophagosomes was found by energy-dispersion X-ray.

CONCLUSIONThe diagnostic signs for Wilson disease are autophagosomes in hepatocytes, cirrhosis accompanied with a few of inflammatory cells. A certain diagnosis of the disease depends on the finding of copper accumulation in hepatocytes.

Adolescent ; Biopsy, Needle ; Child ; Copper ; metabolism ; Female ; Hepatocytes ; metabolism ; Hepatolenticular Degeneration ; diagnosis ; pathology ; Humans ; Liver ; pathology ; ultrastructure ; Male