Sayuri Nakahara

Bilirubin Uridine Diphosphate-Glucuronosyltransferase Variation Is a Genetic Basis of Breast Milk Jaundice

OBJECTIVE To evaluate the role of bilirubin UDP-glucuronosyltransferase family 1, polypeptide A1 (UGT1A1) gene variations on prolonged unconjugated hyperbilirubinemia associated with breast milk feeding (breast milk jaundice [BMJ]). STUDY DESIGN UGT1A1 gene allelic variation was analyzed in 170 Japanese infants with BMJ with polymerase chain reaction-direct sequencing, and their genotypes compared with serum bilirubin concentrations. In 62 of 170 infants, serum bilirubin concentration was followed after 4 months of life. Genotypes were examined in 55 infants without BMJ. RESULTS Of 170 infants with BMJ, 88 (51.8%) were homozygous UGT1A1*6. Serum bilirubin concentrations (21.8 ± 3.65 mg/dL) were significantly greater than in infants with other genotypes (P < .0001). The Gilbert UGT1A1*28 allele was not detected in infants with BMJ, except in an infant who was compound heterozygous with UGT1A1*6. At 4 months of age, serum bilirubin concentration improved to >1 mg/dL, except in 2 infants who were homozygous UGT1A1*7. Homozygous UGT1A1*6 was not detected in the control group. CONCLUSION One-half of the infants with BMJ were homozygous UGT1A1*6 and exhibited a serum bilirubin concentration significantly greater than other genotypes. This finding indicates that UGT1A1*6 is a major cause of BMJ in infants in East Asia. Previous finding have demonstrated that 5β-pregnane-3α,20β-diol present in breast milk inhibits p.G71R-UGT1A1 bilirubin glucuronidation activity. Thus, prolonged unconjugated hyperbilirubinemia may develop in infants with UGT1A1*6 who are fed breast milk.

Neonatal Meckel diverticulum: Obstruction due to a short mesodiverticular band

This is the first report of symptomatic Meckel diverticulum in a newborn, in which direct compression by a short mesodiverticular band (MDB) caused intestinal obstruction. A short MDB can cause intestinal obstruction due to direct compression. There are two mechanisms by which Meckel diverticulum with MDB can cause intestinal obstruction: internal hernia and direct compression. Onset of intestinal obstruction due to direct compression by a short MDB might be earlier than that for internal hernia with long MDB.

Bifidobacterium bifidum OLB6378 Simultaneously Enhances Systemic and Mucosal Humoral Immunity in Low Birth Weight Infants: A Non-Randomized Study

Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity. Administration of Bifidobacterium bifidum OLB6378 (OLB6378) reduced the incidence of late-onset sepsis in infants. In this non-randomized study, we aimed to determine the effect of administration of live OLB6378 on infants’ humoral immunity. Secondly, we tried to elucidate whether similar effects would be observed with administration of non-live OLB6378. Low birth weight (LBW) infants weighing 1500–2500 g were divided into three groups: Group N (no intervention), Group L (administered live OLB6378 concentrate), and Group H (administered non-live OLB6378 concentrate). The interventions were started within 48 h after birth and continued until six months of age. Serum immunoglobulin G (IgG) levels (IgG at one month/IgG at birth) were significantly higher in Group L than in Group N (p < 0.01). Group H exhibited significantly higher serum IgG levels (p < 0.01) at one month of age and significantly higher intestinal secretory immunoglobulin A (SIgA) levels (p < 0.05) at one and two months of age than Group N. No difference was observed in the mortality or morbidity between groups. Thus, OLB6378 administration in LBW infants enhanced humoral immunity, and non-live OLB6378, which is more useful as a food ingredient, showed a more marked effect than the viable bacteria.

Bilirubin Uridine Diphosphate-glucuronosyltransferase Polymorphism as a Risk Factor for Prolonged Hyperbilirubinemia in Japanese Preterm Infants

Objective To determine whether a variant of the bilirubin uridine diphosphate‐glucuronosyltransferase gene (UGT1A1*6) is a risk factor for prolonged hyperbilirubinemia in preterm infants. Study design UGT1A1 genotypes in 46 Japanese preterm infants (<37 weeks of gestation) were compared with UGT1A1 genotypes in 38 control infants, using polymerase chain reaction‐direct sequencing. Prolonged unconjugated hyperbilirubinemia was defined as serum total bilirubin concentration of >150 &mgr;mol/L (8.77 mg/dL) beyond 14 days of life. Results In the case group, 41 of 46 infants (89.1%) had a polymorphic variant, c.211G>A, p.G71R (UGT1A1*6). In the control group, 7 of 38 (18.4%) had UGT1A1*6. The allele frequency of UGT1A1*6 was 0.641 in the prolonged hyperbilirubinemia group, which was significantly higher than in the control group (0.092; P < .001). In total, 39 of 46 infants in the case group were breast fed, and only 10 infants in the control group were breast fed. Conclusions These data suggest that UGT1A1*6 is a risk factor for prolonged unconjugated hyperbilirubinemia in preterm infants in Japan. Given the different rate of breast feeding in this study, additional data are necessary for drawing a definitive conclusion.

Gilbert Syndrome with Concomitant Hereditary Spherocytosis Presenting with Moderate Unconjugated Hyperbilirubinemia

We experienced a case of a 19-year-old man with Gilbert syndrome with concomitant hereditary spherocytosis. The patient presented with moderate unconjugated hyperbilirubinemia, and inherited etiology was strongly suspected. The diagnosis of Gilbert syndrome was confirmed by the genetic analysis of the UGT1A1 gene, demonstrating UGT1A1*28 and compound heterozygote UGT1A1*6. In addition, since the laboratory findings and imaging studies revealed lysemia as well as gallstone and splenomegaly, a diagnosis of hereditary spherocytosis was made as a comorbidity. Both Gilbert syndrome and hereditary spherocytosis are hereditary diseases with a high frequency, and the hyperbilirubinemia may be exacerbated when these two diseases are concomitant.

Hallopeau-Siemens dystrophic epidermolysis bullosa due to homozygous 5818delC mutation in the COL7A gene.

Epidermolysis bullosa (EB) is a group of inherited mechanobullous skin disease. The dystrophic EB (DEB), one subtype of EB, is inherited in an autosomal dominant DEB or in an autosomal recessive (RDEB). DEB is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. Over 300 pathogenic mutations have been detected within COL7A in DEB. Patients with the Hallopeau‐Siemens type (HS‐RDEB), most severe form of DEB, frequently have premature termination codon (PTC) mutations on both alleles. PTC mutations on both alleles result in depleted mRNA and α1 helix, and failure to form the triple helix structure characteristic of type VII collagen. As patients with HS‐RDEB usually have a pair of heterozygous PTC mutations, there have been rarely reported homozygous ones in HS‐RDEB. We report the first case of HS‐RDEB homozygous PTC mutations of 5818delC in both COL7A1 alleles. This case report suggests the positional effect of PTC mutations and vigilance against early infantile death in EB including HS‐RDEB.

Suspected fetal onset of neonatal transient eosinophilic colitis and development of respiratory distress.

Neonatal transient eosinophilic colitis (NTEC) is a new disease concept within eosinophilic gastroenteritis, which was proposed by Ohtsuka et al. It causes hematochezia as a result of eosinophilia, in neonates who have not yet started to receive enteral nutrition, although the whole‐body status of the infant is in fact relatively good. To date, there have been no reports of this disease in which abnormalities were noted during gestation, and the clinical phenomena surrounding it, along with any complications, are not yet clear. We encountered a suspected case of NTEC causing respiratory distress with aspiration of hematochezia, in which dilated bowel was noted during gestation. This case indicates that NTEC may occur at the fetal stage and be complicated by respiratory distress.

Efficacy of bronchial fiberscope in esophageal fistula caused by necrotizing bronchitis

Neonatal necrotizing bronchitis is a disease that occurs in premature and low‐birthweight infants who are subject to artificial respiratory management, and which has a poor prognosis, because it progresses suddenly and can result in death. There have been no reports of survival to date in cases of tracheo‐esophageal fistula caused by necrotizing bronchitis, and no swift and effective management method has yet been reported. This report describes a case in which the use of a bronchial fiberscope in making an early diagnosis facilitated appropriate management and survival. The proactive use of a bronchial fiberscope in regard to this disease, which has a high fatality rate, may save lives.