Biliary lipid metabolism in children with chronic intrahepatic cholestasis

Biliary lipid composition, standard liver function tests, serum lipids and faecal fat excretion were studied in 15 children with chronic intrahepatic cholestasis (severe intrahepatic cholestasis, n=6; paucity of intralobular bile ducts, n=4; benign recurrent cholestasis, n=5) and compared to 15 children without gastrointestinal diseases. Severe and benign intrahepatic cholestasis were associated with normal or moderately elevated serum lipids. Biliary lipid concentrations were extremely reduced, bile acid concentrations were below the critical micellar concentration. This may account for the high incidence of gallstone formation in these patients. Remission periods in patients with benign recurrent cholestasis were not followed by complete normalisation of biliary lipid concentrations, indicating a primary defect in hepatic excretory function. Children with paucity of intralobular bile ducts showed markedly increased serum lipids, but only a two-fold reduction in biliary lipid concentrations. Cholic acid was the predominant bile acid in bile of all cholestatic children even during remission. Neither increased levels of monohydroxy bile acids nor unusual bile acids could be identified in notable amounts.     

Neonatal cholestasis associated with fetal arrhythmia

We evaluated the consequence of different types of fetal arrhythmia in the development of neonatal cholestasis. The charts of 38 children born at St. Justine Hospital between 1993 and 2001 with sustained and hemodynamically significant fetal arrhythmias were studied: 19 with supraventricular tachycardia, 14 with atrial flutter, and 5 with atrio-ventricular (AV) block. Six of these 38 children presented with cholestasis. The average duration of arrhythmia was 15.7 days in the noncholestatic group, compared with 40.3 days in the cholestatic group ( P <.05). The three infants with supraventricular tachycardia who developed cholestasis survived and resolved their cholestasis, whereas 2 of 3 infants with AV block died. No infant with atrial flutter developed cholestasis. We conclude that newborns who developed tachyarrhythmia during their fetal life can show transient neonatal cholestasis. In patients with AV block, severe and irreversible liver failure could be observed. In addition, extensive collapse of the stroma and the absence of hepatocytes (foie vide) also were observed in a patient with anti-Ro antibodies.     

Risk factors for neonatal hyperglycemia associated with 10% dextrose infusion

As part of an intensive drug surveillance program, we identified rates and associated risk factors for hyperglycemia related to intravenous 10% dextrose solution in a population of 1,157 newborns in two neonatal intensive care units. Hyperglycemia related to 10% dextrose solution was observed in 64 exposed infants (5.5%), a rate similar to that observed for hypoglycemia (6.7%) in this population. There was a highly significant trend toward an increasing risk of hyperglycemia with decreasing body weight, such that the risk of hyperglycemia among infants weighing less than 1,000 g was 18 times greater than the risk among infants weighing more than 2,000 g. The risk of hyperglycemia also increased with increasing dextrose dose. The effects of weight and dose were independent. Certain measures of disease severity also were associated with increased risks of hyperglycemia. Because increases in blood glucose levels may affect renal function or possibly lead to intraventricular hemorrhage, it is important that glucose levels in neonates receiving 10% dextrose solution be carefully monitored, and the total dextrose dose be adjusted accordingly.     

Painless cholestasis in Kawasaki syndrome associated with pancreatitis

Painless cholestasis and hydrops of the gallbladder may occur as secondary symptoms in Kawasaki syndrome. Surgical treatment is rarely indicated. Our case report confirms the validity of this conservative approach. In addition, during the course of the disease we observed a pancreatitis without severe symptoms; this has not been described in connection with mucocutaneous lymph node syndrome to date. Correspondence to: C. Petersen     

Biliary atresia and meconium ileus associated with Niemann-Pick disease

A boy, and 10 months later his sister, presented in the neonatal period with meconium ileus. Both became jaundiced and were found to have biliary atresia and Niemann-Pick disease, type C. The causes of the meconium ileus were not established. Both died before the age of 6 weeks.     

Biliary atresia with associated complicated anorectal and urogenital malformations

We report on a girl with biliary atresia (BA) who also suffered with anorectal agenesis without fistula and complicated urogenital malformation. The outcome of patients with these severe anomalies is poor, but she has survived without liver and/or renal transplantation for more than 3 years. A careful treatment plan for each anomaly in addition to prevention of cholangitis and urinary tract infection is indispensable for managing these complicated anomalies.     

Intrahepatic cholestasis associated with parenteral nutrition in premature infants.

Sixty-two premature infants less than 2,000 gm birth weight received parenteral nutrition (PN) during periods of respiratory distress with feeding intolerance. Intrahepatic cholestasis (direct bilirubin greater than or equal to 1.5 mg/dl) associated with PN developed in 14 or 23% of these infants. The mean time on PN to onset of cholestasis was 42 days, and the cholestasis persisted as long as the infants continued to receive PN. All five infants who had serial follow-up laboratory studies showed an eventual return of direct bilirubin levels to normal. The direct bilirubin level appeared to be the best clinically available test to monitor for the onset and to follow the resolution of this complication. The very low birth weight infants less than 1,000 gm appeared to be at an increased risk of developing cholestasis with an incidence of 50%. However, there was no correlation between the length of time PN was administered to onset of cholestasis and the gestational age or birth weight of the infants. These tiny premature infants also received PN for significantly longer periods of time, and the longer the infusions were administered the greater was the risk of cholestasis developing.     

Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis

We report a novel glucose-6-phosphate dehydrogenase (G6PD) mutation, which we propose to name G6PD Cincinnati (c.1037A > T, p.N346I), found in combination with G6PD Gastonia (c.637G > T, p.V213L) in an infant who presented with neonatal cholestasis. The G6PD Cincinnati mutation results in a non-conservative amino acid substitution at the tetramer interface disturbing its formation, as seen by native gel electrophoresis and immunoblotting. G6PD Gastonia disrupts dimerization of the enzyme and by itself causes chronic non-spherocytic hemolytic anemia. The G6PD Cincinnati mutation may have aggravated the clinical picture of G6PD Gastonia with the result of severe perinatal hemolysis causing cholestasis and associated liver injury.     

Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs'negative haemolytic anaemia

We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs'negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum γ-glutamyl transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we detected large amounts of 1β-hydroxylated bile acids, especially lβ,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid (25.5-67.9% of total urine bile acids) in the urine during phenobarbital therapy. However, the amount of urinary 1β-hydroxylated bile acids gradually decreased as the disease progressed. At the end-stage, we detected large amounts of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The ratio of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end-stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of Δ⁴-3-oxo bile acids is increased. Familial intrahepatic cholestasis, Coombs'negative haemolytic anaemia, 1β-hydroxylated bile acids, unsaturated ketonic bile acids     

新生儿肠外营养相关胆汁淤积因素612例分析

目的为提高危重新生儿肠外营养支持的安全性和有效性提供依据。方法对1985．4—2005．3行5d以上静脉营养支持的612例住院新生儿资料进行分析。612例分为甲组（1985．4—1995．3）和乙组（1995．4—2005．3）。其中甲组70例再分为肠外营养相关胆汁淤积组（PNAC组）6例和非PNAC组64例,乙组542例也分为PNAC组12例和非PNAC组530例。比较甲乙两组新生儿PNAC发生率及相关因素。结果接受5d以上静脉营养支持的新生儿PNAC总发生率为2．94％,甲组PNAC发生率为8．57％,乙组发生率为2．21％,后10年PNAC发病率有明显下降（OR值为0．242,95％CI为0．088～0．666）。PNAC组的胎龄、出生体重均小于非PNAC组（其中胎龄33±5周比（36±4）周,P=0．009;OR值为0．827,95％CI为0．698～0．980。出生体重2003g±743g比2393g±764g,P=0．045;OR值为1．001,95％CI为0．999～1．002）,而平均PN持续时间、热卡摄入量均大于非PNAC组（其中PN持续时间32d±30d比13d±10d,P=0．000;OR值为1．072,95％c,为1．032～1．112。PN摄入量（272±46）kJ／（kg·d）[（65．0±10．9kcal／（kg·d）,（1kcal=4．184kJ）]比（232±55）kJ／（kg·d）[（55．5±13．1）kcal／（kg·d）],P=0．002;OR值为1．066,95％CI为1．012～1．122）。非PNAC组体重增加与PNAC组相比有增加趋势[（20±27）g／d比（9±19）g／d,P=0．175]。结论PNAC发生与早产、低出生体重、PN持续时间超过2周、PN提供的热卡量过高有关。     

Comparison of the catabolism of branched-chain L-amino acids in cultured human skin fibroblasts

Using 1-14C-labeled substrates, the metabolism of naturally occurring branched-chain L-amino acids was studied in incubations with cultured human skin fibroblasts derived from normal subjects and from a patient with maple syrup urine disease (variant form). Practically saturating conditions were reached at 1 mmol/liter of substrate and metabolic rates remained essentially constant up to 120 min. In control fibroblasts, the transamination of 14C-labeled leucine, valine, isoleucine, and allo-isoleucine (1 mmol/liter) was about 26, 13, 12, and 5 nmol/90 min/mg of cell protein, respectively. The portion of transamination products undergoing oxidative decarboxylation within the cells was about 17, 43, 34, and 23%, respectively. With the maple syrup urine disease cell line, comparable transamination rates were found. As compared to the findings with normal cells, however, 14CO2 production from the above mentioned substrates was reduced and amounted to 14, 11, 25, and 45%, respectively. Thus it appeared that residual branched-chain 2-oxo acid dehydrogenase activity was differently reduced towards the four 2-oxo acid substrates.