Measures for food allergy emergency in nurseries.

Background: As food allergy potentially can induce life-threatening anaphylaxis, measures for food allergy are required at nurseries caring for food allergy children, but a large-scale factual investigation has not been carried out. Objective: We evaluated measures for food allergy emergency in nurseries. Methods: A questionnaire survey regarding emergency measures in all authorized nurseries (411 facilities including 20,586 children) was conducted in Kawasaki city, Japan. Results: The recovery rate of the questionnaire was 46.5%, which include 14,343 children of 191 facilities in total. A total of 637 children (4.4%) in 157 facilities (82.2%) requires elimination diets that were suggested by physicians. Among them, 22 children had been suggested to undergo the use of epinephrine auto-injection kit for emergency. 161 facilities (84.3%) had set a specific manual for emergency of food allergy. Emergency cases over the past one year were 4 cases and there was no case that had been suggested to use epinephrine auto-injection kit. All were anaphylaxis and the causes of these included 2 accidental digestion of culprit foods and the causes of other 2 cases were unknown. A case who required no elimination diet showed first episode of anaphylaxis. All cases were recovered. Conclusion: High percentage of nurseries in Kawasaki city has cared for food allergy children. While many children with food allergy have been in nurseries, only several cases of anaphylaxis have been reported for a 1 year. Among 4 cases of anaphylaxis, no specific cause has been recognized in 2 cases and 1 case has been the first episode of anaphylaxis. While most of nurseries have set specific measures for emergency of food allergy, there is certain possibility that nursery staffs can encounter the first episode of anaphylaxis even if there is no food allergy child. For all nurseries, emergency measures for food allergy are vital.

Hepatitis B virus DNA in the fingernails and hair of children with acute hepatitis B.

Hepatitis B virus (HBV) DNA is detectable in the nails and hair of patients with chronic HBV infection. However, it remains unclear whether HBV DNA can be detectable in the nails and hair of patients with acute HBV infection. We encountered two cases of children with acute HBV infection. HBV DNA in the nails and hair from the two children was evaluated by real-time PCR. To clarify the characteristics of HBV DNA, full-length HBV genome sequencing and phylogenetic tree analysis were performed. The levels of serum HBV DNA in children of cases 1 and 2 at day 0 were 7.6 Log IU/mL and 7.4 Log IU/mL, respectively. Nail HBV DNA was detected in both children (case 1: 4.6 Log IU/mL at day 0, case 2: 5.5 Log IU/mL at day 14). Moreover, hair HBV DNA was detectable in case 2 (4.0 Log IU/mL at day 14). Serum HBV DNA became undetectable within approximately 3-4 months after the first hospital visit. After the resolution of HBV viremia, nail and hair HBV DNA became undetectable. The sequence analysis of serum, nail and hair HBV DNA showed the same HBV genotype in each case (case1: genotype C, case 2: genotype A). In case 1, 3 nucleotides were different in the full-genome HBV sequence between the serum and nails. In case 2, the full-genome HBV sequences were identical among the serum, nails and hair. In conclusion, HBV DNA was detectable in nails and hair of children with acute HBV infection.

Bile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment.

BACKGROUND: We encountered 7 Japanese patients with bile acid synthesis disorders (BASD) including 3ß-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase (3ß-HSD) deficiency (n = 3), Δ4-3-oxosteroid 5ß-reductase (5ß-reductase) deficiency (n = 3), and oxysterol 7α-hydroxylase deficiency (n = 1) over 21 years between 1996 and 2017. AIM: We aimed to clarify long-term outcome in the 7 patients with BASD as well as long-term efficacy of chenodeoxycholic acid (CDCA) treatment in the 5 patients with 3ß-HSD deficiency or 5ß-reductase deficiency. METHODS: Diagnoses were made from bile acid and genetic analyses. Bile acid analysis in serum and urine was performed using gas chromatography-mass spectrometry. Clinical and laboratory findings and bile acid profiles at diagnosis and most recent visit were retrospectively obtained from medical records. Long-term outcome included follow-up duration, treatments, growth, education/employment, complications of treatment, and other problems. RESULTS: Medians with ranges of current patient ages and duration of CDCA treatment are 10 years (8 to 43) and 10 years (8 to 21), respectively. All 7 patients, who had homozygous or compound heterozygous mutations in the HSD3B7, SRD5B1, or CYP7B1 gene, are currently in good health without liver dysfunction. In the 5 patients with CDCA treatment, hepatic function gradually improved following initiation. No adverse effects were noted. CONCLUSIONS: We concluded that CDCA treatment is effective in 3ß-HSD deficiency and 5ß-reductase deficiency, as cholic acid has been in other countries. BASD carry a good prognosis following early diagnosis and initiation of long-term CDCA treatment.

Chronic hepatitis without hepatic steatosis caused by citrin deficiency in a child.

Citrin deficiency manifests as both neonatal intrahepatic cholestasis (NICCD) during early infancy and adult-onset type II citrullinemia during adulthood. Hepatic steatosis is most frequently observed in patients with citrin deficiency. Thus, non-alcoholic fatty liver disease that is unrelated to being overweight is considered one of the clinical features of citrin deficiency in children and adults. However, it remains unknown whether citrin deficiency is a cause of chronic hepatitis in the absence of fatty changes to the liver that occur during childhood. We encountered an 8-year-old girl who showed no clinical features of NICCD during infancy and had persistently elevated transaminase levels for several years. Liver biopsy showed widening of the portal tracts with intense mononuclear cell infiltration and mild fibrosis but no fatty changes. However, she had peculiar dietary habits similar to those that have been observed in many patients with citrin deficiency. In addition, a slightly elevated plasma citrulline level and a high pancreatic secretory trypsin inhibitor level were detected by blood examination, and she was diagnosed with citrin deficiency. Analysis of the SLC25A13 gene revealed the presence of the compound heterozygous mutations 851del4 and IVS13 + 1G > A. Thus, citrin deficiency should be included in the differential diagnosis of chronic hepatitis in children, even in the absence of hepatic steatosis.

Molecular genetic and bile acid profiles in two Japanese patients with 3beta-hydroxy-DELTA5-C27-steroid dehydrogenase/isomerase deficiency.

We report definitive diagnosis and effective chenodeoxycholic acid (CDCA) treatment of two Japanese children with 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum [gamma]-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3[beta]-hydroxy-[DELTA]5 bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified four novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in one allele. Excessive 3[beta]-hydroxy-[DELTA]5-bile acids such as 3[beta],7[alpha]-dihydroxy- and 3[beta],7[alpha],12[alpha]-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3[beta]-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids were still detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with CDCA treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of CDCA treatment at this critical time, before the late cholestatic stage.

Severe pulmonary emphysema in a girl with interstitial deletion of 2q24.2q24.3 including ITGB6.

Owing to the large size of chromosome 2, partial monosomy of the long arm of this chromosome gives rise to many specific phenotypes. We report on a 2-month-old girl with an interstitial deletion of 2q24.2q24.3, which was confirmed by microarray-based comparative genomic hybridization analysis. The patient showed delayed growth and mental retardation, early myoclonic seizures, and characteristic dysmorphic features including thick arched eyebrows, upslanting palpebral fissures, long eyelashes, depressed nasal bridge, short nose, long philtrum, small mouth, micrognathia, and low set ears. Her early myoclonic seizures were likely due to haploinsufficiency of SCN1A and SCN2A, which are included in the deletion region. When she experienced acute bronchopneumonia, she showed severe pulmonary emphysema. The deletion region of 2q24.2 includes the integrin beta6 gene (ITGB6), which may prevent acute lung injury and pulmonary emphysema. Many previously reported patients with deletions of 2q24.2 showed poor outcomes because of respiratory failure. These observations suggest the possibility of a strong relationship between haploinsufficiency of ITGB6 and pulmonary dysfunction.