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An instructive case of isolated congenital folate malabsorption provides insight into the understanding of this rare disease. Folate loading tests with both timed serum and cerebrospinal fluid folate determinations suggest that both of the two mechanisms involved in gastrointestinal folate absorption are defective in this condition. [ABSTRACT FROM AUTHOR]

Background: We determined types of peer-reviewed articles that cited Pediatrics case reports and whether citations were "appropriate" or "inappropriate.", Methods: The 20 most highly cited Pediatrics case reports published between January 2011 and April 2016 were identified. All articles referencing these 20 case reports were analyzed for appropriateness of the citation. Appropriate citations referred to the original article specifically as a case report or cited the case report in support of general knowledge. Inappropriate citations used case reports to infer causation, support proof of mechanism, or were deemed irrelevant to claims being supported. Two authors independently coded all citations., Results: These 20 case reports were cited in 479 articles (median: 24 citations per case report). In most articles (83.6%, n = 367), case reports were cited appropriately; in 53.4% ( n = 196) of articles, a case report was specifically referred to, and in 46.6% ( n = 171) of articles, the case report was used to support general knowledge. For inappropriate citations, in 63.3% ( n = 50) of articles, case reports were used to infer causation; in 15.2% ( n = 12) of articles, they were used as proof of mechanism of pathogenesis or treatment; and in 21.5% ( n = 17) of articles, they were irrelevant. Case reports were most commonly cited in review articles (38.7%, n = 170) and original studies (31%, n = 136). "Original studies" were articles in which authors reported original data, excluding case reports., Conclusions: These results reveal that most citations of Pediatrics case reports are appropriate., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Malatack is the section editor for case reports in Pediatrics. Dr Sisk was previously the editorial fellow for Pediatrics; Dr Collins and Ms Dillenbeck have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Malatack is a member of the editorial board of Pediatrics and is the Case Reports section editor.

Progressive familial cholestasis type 2 is caused by a genetically determined absence or reduction in the activity of the bile salt export pump (BSEP). Reduction or absence of BSEP activity causes a failure of bile salt excretion, leading to accumulation of bile salts in hepatocytes and subsequent hepatic damage. Clinically, patients are jaundiced, suffer from severe intractable pruritus, and evidence progressive liver dysfunction. A low level of serum γ-glutamyl transpeptidase, when associated with the described signs and symptoms, is often an early identifier of this condition. Treatment options to date include liver transplantation and the use of biliary diversion. We report a multidrug regimen of 4-phenylbutyrate, oxcarbazepine, and maralixibat (an experimental drug owned by Shire Pharmaceuticals, Dublin, Republic of Ireland) that completely controlled symptoms in 2 siblings with partial loss of BSEP activity., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Malatack serves as Case Reports editor for Pediatrics but did not participate in the peer review process of this Case Report as a result of being an author; and Dr Doyle has indicated he has no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objective: To determine if immunomodulatory treatment including intravenous immunoglobulin (IVIG) can favorably affect survival in neontatal hemochromatosis (NH) diagnosed postnatally because it can effectively prevent occurrence of NH when applied during gestations at risk., Study Design: We treated 16 newborn infants with liver failure due to NH with high-dose IVIG, in combination with exchange transfusion in 13 (ET/IVIG), and compared the outcome with 131 historical controls treated conventionally., Results: The severity of liver disease as estimated by prothrombin time was similar in the subjects receiving ET/IVIG and the historical controls, and the medical therapy was equivalent with the exception of the ET/IVIG therapy. Twelve subjects (75%) had good outcome, defined as survival without liver transplantation, whereas good outcome was achieved in only 17% (23/131) of historical control patients (P < .001). Four subjects died, 2 without and 2 after liver transplant. Survivors were discharged 6 to 90 days after receiving ET/IVIG therapy, and those followed for more than 1 year are within normal measures for growth, development, and liver function., Conclusions: Immune therapy with ET/IVIG appears to improve the outcome and reduce the need for liver transplantation in patients with NH.

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by impaired intestinal folate absorption and impaired folate transport into the central nervous system. Recent studies in 1 family revealed that the molecular basis for this disorder is a loss-of-function mutation in the PCFT gene encoding a proton-coupled folate transporter. The current study broadens the understanding of the spectrum of alterations in the PCFT gene associated with HFM in 5 additional patients. There was no racial, ethnic, or sex pattern. A total of 4 different homozygous mutations were detected in 4 patients; 2 heterozygous mutations were identified in the fifth patient. Mutations involved 4 of the 5 exons, all at highly conserved amino acid residues. A total of 4 of the mutated transporters resulted in a complete loss of transport function, primarily due to decreased protein stability and/or defects in membrane trafficking, while 2 of the mutated carriers manifested residual function. Folate transport at low pH was markedly impaired in transformed lymphocytes from 2 patients. These findings further substantiate the role that mutations in PCFT play in the pathogenesis of HFM and will make possible rapid diagnosis and treatment of this disorder in infants, and prenatal diagnosis in families that carry a mutated gene.

Lysosomal storage diseases are a group of disorders which have in common an inherited defect in lysosomal function-in most cases, a missing intralysosomal enzyme. Research into potential treatment options for this group of disorders has focused on enzyme replacement. Over the past two decades, hematopoietic stem cell transplantation has been used with increasing frequency to treat patients with lysosomal storage disease by providing a population of cells with the capacity to produce the missing enzyme. The success of marrow transplantation depends on the specific enzyme deficiency and the stage of the disease. Generally, visceral symptoms can be improved, whereas skeletal lesions remain relatively unaffected. The effect on neurologic symptoms varies. Hematopoietic stem cell transplantation remains a viable treatment option in those lysosomal storage diseases where data supportive of disease stabilization or amelioration are known. Early transplantation is the goal so that enzyme replacement may occur before extensive central nervous system injury becomes evident. When inadequate clinical data are available, the decision to perform transplantation requires experimental data demonstrating that the enzyme in question is both excreted from normal cells and taken up by affected cells as evidenced by elimination of storage material in vitro.

We have identified a constitutional inversion in chromosome 5 associated with familial adenomatous polyposis in three generations of a Mexican family. Two of three siblings developed hepatic neoplasia in infancy. The gene truncation assay failed to demonstrate a truncated protein in the segment harboring the adenomatous polyposis coli (APC) genes. Polymerase chain reaction (PCR) amplification of APC gene coding exons and sequencing of PCR products did not reveal any significant mutation. The data suggest that in this family, the phenotype may be the result of a "position effect."

Background: Previous studies have demonstrated that in the emergency treatment of an asthma exacerbation, corticosteroids used in conjunction with beta-agonists result in lower hospitalization rates for children and adults. Furthermore, orally administered corticosteroids have been found to be effective in the treatment of outpatients with asthma. However, similar data in inpatients is lacking., Objective: The purpose of this study was to determine the efficacy of oral prednisone versus intravenous methylprednisolone in equivalent doses for the treatment of an acute asthma exacerbation in hospitalized children., Methods: We conducted a randomized, double-blind, double-placebo study comparing oral prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a group of patients 2 through 18 years of age hospitalized for an acute asthma exacerbation. All patients were assessed by a clinical asthma score 3 times a day. The main study outcome was length of hospitalization; total length of stay and time elapsed before beta-agonists could be administered at 6-hour intervals. Duration of supplemental oxygen administration and peak flow measurements were secondary outcome measures., Results: Sixty-six patients were evaluated. Children in the prednisone group had a mean length of stay of 70 hours compared with 78 hours for the methylprednisolone group (P =.52). Children in the prednisone group were successfully weaned to beta-agonists in 6-hour intervals after 59 hours compared with 68 hours for the methylprednisolone group (P =.47). Patients receiving prednisone required supplemental oxygen for 30 hours compared with 52 hours for the methylprednisolone group (P =.04)., Conclusion: There was no difference in length of hospital stay between asthmatic patients receiving oral prednisone and those receiving intravenous methylprednisolone. Because hospitalization charges are approximately 10 times greater for intravenous methylprednisolone compared with oral prednisone, the use of oral prednisone to treat inpatients with acute asthma would result in substantial savings.

Objective: To report the clinical experience of three patients with fever of unknown origin ultimately diagnosed as having cat-scratch granulomatous hepatitis in the absence of peripheral adenopathy., Design: Case-control study., Setting: Referral center at university-based referral practice., Patients: Three children with fever of unknown origin. Follow-up following presentation was 6 months for each patient., Measurement and Results: All three patients with fever of unknown origin were diagnosed radiographically to have multiple hepatic defects. The defects were shown histologically to be granulomatous. Two of the three patients had Warthin-Starry staining bacilli in the granulomas consistent with a diagnosis of Afipia felis. All three had positive cat-scratch skin test results., Conclusions: Cat-scratch disease in the absence of peripheral adenopathy is a heretofore unrecognized cause of fever of undetermined origin and may account for a small, but significant, percentage of children presenting with it.

Oral-facial-digital syndrome type I is a group of X-linked dominant conditions, lethal in utero in male individuals. Internal anomalies are less well documented than are external findings. We report a case of typical phenotype and absent family history of kidney disease in a 15-year-old white girl (46,XX) who died of renal failure and massive cerebral hemorrhage. At necropsy, the kidneys were greatly enlarged but of fairly normal shape. The cortex was replaced by thin-walled spherical cysts, 0.5 to 2.0 cm in diameter; the majority of the smaller cysts were located deep in the cortex, and the medulla contained lesser numbers of larger cysts. No distal urinary tract obstruction was present. Microdissection revealed cysts and diverticula located in all segments of the nephrons and collecting ducts. Uninvolved nephrons showed diffuse hypertrophy. These findings were correlated with immunoperoxidase stains using peanut lectin, Lotus tetragonolobus agglutinin, antibodies to cytokeratins, stage-specific embryonic antigen-1, Tamm-Horsfall protein, and epithelial membrane antigen. Other visceral anomalies included biliary cystadenomatous proliferation in the liver and pancreatic cysts. The renal changes are similar to those of autosomal dominant (adult-type) polycystic disease.

Cyclosporine is a potent immunosuppressive drug, which has dose-related nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Long-term survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twenty-nine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity.

During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 months to 18 years) underwent orthotopic liver transplantation using cyclosporine and prednisone. Major indications were biliary atresia/hypoplasia, and metabolic liver disease. Thirty-two of 138 patients evaluated for the procedure died prior to transplantation. Thirty patients are alive from 6 to 29 months later including 7/15 patients who required retransplantation. Twenty-one of 32 patients are alive at 1 year following initial transplantation. All 30 survivors are clinically well and living at home; only one has an abnormal bilirubin level. Serious, life-threatening medical and surgical complications were common during the early months following transplantation. With one exception, deaths and major rejection episodes occurred early (before 120 days). All survivors are relieved of the stigmata of chronic liver disease, and many have demonstrated catch-up growth. Liver transplantation is an effective treatment for end-stage pediatric liver disease.

Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.

Acute hepatic failure developed in four patients (aged 7 to 13 months) who had extrahepatic biliary atresia treated initially by portoenterostomy. Two were stable outpatients with minimal jaundice, while the other two were hospitalized for metabolic or nutritional complications. Postmortem examination in each patient revealed massive acute hepatic infarction with few surviving hepatocytes. In all cases, the hepatic failure had been preceded by an episode of hypotension and/or hypovolemia. The exact pathogenesis of the infarction remains unclear but it may be related to decreased hepatic blood flow secondary to biliary obstruction. The only effective treatment for these patients is intensive supportive care and urgent liver transplantation.

Between March 3, 1981, and June 1, 1984, 216 children were evaluated for orthotopic liver transplantation. Of the 216 patients, 117 (55%) had received at least one liver transplant by June 1, 1985. Fifty-five (25%) died before transplantation. The 117 patients who received transplants were grouped according to severity of disease and degree of general decompensation at the time of transplantation. The severity of a patient's medical condition with the possible exception of deep hepatic coma, did not predict outcome following orthotopic liver transplantation. Seventy variables were assessed at the time of the evaluation. Twenty-three of the 70 variables were found to have prognostic significance with regard to death from progressive liver disease before transplantation. These 23 variables were incorporated into a multivariate model to provide a means of determining the relative risk of death among pediatric patients with end-stage liver disease. This information may allow more informed selection of candidates awaiting liver transplantation.

Echocardiographic studies were performed in 73 patients with various types of chronic liver disease. They were 0.5 to 19 years old (mean 5). Thirteen patients underwent follow-up echocardiography 1 to 13 months (mean 6) after liver transplantation. Preoperatively 60 patients (82%) showed evidence of high cardiac output (cardiac index greater than 4 liters/min/m2); these patients manifested increased left ventricular (LV) and left atrial dimensions and a thickened LV posterior wall. Transvenous contrast echocardiographic study confirmed the presence of intrapulmonary arteriovenous shunting in 4 patients. Studies after liver transplantation revealed a reduced LV end-diastolic dimension in 12 patients. Cardiac index was reduced a mean of 35% after transplantation (p less than 0.001). This study suggests that liver transplantation improves common hemodynamic abnormalities in chronic liver disease.

In a 36-month period from 1981 to 1984, 209 pediatric patients were evaluated for liver transplantation. The purpose of the evaluation was to assess the severity and progression of the disease, anatomical suitability for transplantation, and psychosocial stability and to initiate family education. Of the 209 patients evaluated, 85 (41%) underwent transplantations and 64 (75%) survived at least 12 months. Thirty-four (16%) patients were not considered candidates for transplantation. The mean waiting period increased from 80.3 days to 232 days. Of 174 patients considered for transplantation, 41 (24%) died prior to surgery. A formal evaluation for liver transplantation permitted appropriate selection of candidates and provided education for informed consent. We also stress the need for greater participation in pediatric organ donation.