Mutations in bile salt export pump (ABCB11) in two children with progressive familial intrahepatic cholestasis and cholangiocarcinoma.

Fatal peripheral cholangiocarcinoma developed in 2 girls with progressive familial intrahepatic cholestasis, ABCB11 mutations, and absent bile salt export pump (BSEP) expression. BSEP deficiency may cause cholangiocarcinoma through bile-composition shifts or bile-acid damage within cells capable of hepatocytic/cholangiocytic differentiation. This observation suggests the need for hepatobiliary-malignancy surveillance and early consideration for liver transplantation.

Hepatic veno-occlusive disease in ataxia-telangiectasia.

Existing descriptions of liver abnormalities in ataxia-telangiectasia have been associated with co-existent hepatitis virus infection. Here we report veno-occlusive disease of the liver in 2 patients with ataxia telangiectasia that is not attributable to bone marrow transplantation or coincidental hepatitis infection.

Medical complications in long-term survivors with X-linked myotubular myopathy.

OBJECTIVES: X-linked myotubular myopathy (MTM1) is a rare developmental disorder of skeletal muscle characterized by the presence of central nuclei in biopsy specimens from affected male subjects. Until recently, the disorder was usually fatal within the first year of life. This study was undertaken to determine the outcome in long-term survivors (>1 year of age) with MTM1. METHODS: Clinical data were obtained on 55 male subjects from 49 independent North American families for which a mutation was identified in the X-linked myotubularin gene by direct genomic sequencing. Medical records were reviewed and families were interviewed to ascertain features at birth, length of survival, developmental milestones, and medical complications. RESULTS: Seventy-four percent (26 of 35) of the affected male subjects over the age of 1 year are living (range, 1 to 27 years); 80% remain completely or partially ventilator-dependent. In the absence of significant hypoxia, cognitive development is normal, and the muscle disorder appears nonprogressive. Several patients have had other medical problems not previously reported to be associated with MTM1. These include pyloric stenosis (4 male subjects from 3 families), spherocytosis (2 patients), gallstones (4 patients), kidney stones or nephrocalcinosis (2 patients), a vitamin K responsive bleeding diathesis (2 patients), and height >/=90% for age (40% of the patients). Six patients have had biochemical evidence of liver dysfunction, and 2 patients died after significant liver hemorrhage. CONCLUSIONS: These data suggest that the prognosis for X-linked MTM may not be as poor as previously reported. However, at least some long-term survivors appear at risk for medical complications involving other organ systems, and patients should be carefully monitored for these potentially life-threatening complications. The pleiotropic symptoms demonstrated in these patients strongly suggest that the function of the MTM1 protein is not limited to developing muscle cells.

Extraintestinal rotavirus infections in children with immunodeficiency.

Some rotavirus strains, including vaccine candidates, have been demonstrated to cause hepatitis in immunodeficient and malnourished mice and to grow in human liver cells. To determine whether rotavirus spreads outside the intestine in naturally infected children, we examined tissues from four immunodeficient children affected with severe combined immunodeficiency disease, acquired immunodeficiency disease syndrome, or DiGeorge syndrome. Chronic rotavirus-related diarrhea, which persisted until death, had also developed in each child. Using indirect immunoperoxidase techniques, we identified rotavirus antigen in the liver and kidney with a hyperimmune guinea pig antiserum prepared to double-shelled rotavirus particles. Similar immunostaining with an antiserum to a rotavirus nonstructural protein (NS26) provided evidence of active virus replication. The observed reactivity was eliminated specifically when serial sections were immunostained with the same antiserum that had been absorbed with either double-shelled rotavirus particles or NS26. Immunostaining was not observed in the liver of children with other diseases (alpha 1-antitrypsin deficiency, inspissated bile syndrome, and acute rejection of a transplanted liver). These findings demonstrate that rotavirus infections in children can extend beyond the intestinal tract. Further studies are warranted to determine whether extraintestinal rotavirus replication occurs in children without severe immunodeficiency, such as malnourished children.

Liver transplantation for cholesteryl ester storage disease.

This case describes a patient with cholesteryl ester storage disease who underwent liver transplantation for progressive cirrhosis, portal hypertension, ascites, and uncontrollable gastrointestinal bleeding. Four and one-half years posttransplant, her growth improved, cholesterol levels have returned to normal, and she is clinically well except for mild hypersplenism and an elevated blood urea nitrogen (BUN) and creatinine. Serum triglycerides remain elevated, but there have been no signs of progressive renal, intestinal, vascular, or pulmonary disease.

Cholestasis in immature newborn infants: is parenteral alimentation responsible?

This report is a response to the suggestion, first raised in The Journal in 1971, 1 that intravenous alimentation may be responsible for intrahepatic cholestasis in premature infants. Nine of 15 premature infants (30 weeks' gestation or less, birth weight up to 1,250 gm) who survived at least five days and were autopsied were found to have cholestasis. The most severe hepatic pathology was found in the infants whose nutrition was poorest and whose livers were smallest. Both groups had a variety of other clinical problems, especially respiratory distress, intracranial hemorrhage, and infection; it was the first of these that prevented oral feeding in most instances. No correlation was found between treatment with intravenous FreAmine and/or Intralipid and the presence of cholestasis. None of the affected patients, however, could sustain oral or nasogastric feedings during the first seventeen days of life, whereas all surviving patients without cholestasis were able to feed orally within eight days. Fasting later in the course had no effect. Therefore, early fasting, rather than parenteral supplementation, may contribute to impaired hepatobiliary function in the small premature infant.