(Epi)genetic and clinical characteristics in 84 patients with pseudohypoparathyroidism type 1B.

OBJECTIVE: Pseudohypoparathyroidism type 1B (PHP1B) caused by methylation defects of differentially methylated regions (DMRs) on the GNAS locus can be categorized into groups according to etiologies and methylation defect patterns of the DMRs. The aim of this study was to clarify the clinical characteristics of each group. DESIGN: Comprehensive molecular analyses consisting of methylation, copy number, and microsatellite analyses. METHODS: Eighty-four patients with PHP1B were included in this study. We classified them into 5 groups, namely, autosomal dominant inheritance-PHP1B (Group 1, G1), sporadic-PHP1B (G2), and atypical-PHP1B (G3-G5), based on the methylation defect patterns in 4 DMRs on the GNAS locus and etiologies and evaluated the clinical findings in each group and compared them among the groups. RESULTS: G2 had the youngest age and the highest serum intact parathyroid hormone levels among the 5 groups at the time of diagnosis. The most common symptoms at the time of diagnosis were tetany in G1, and seizures or loss of consciousness in G2. Albright's hereditary osteodystrophy and PHP-suggestive features were most frequently observed in the G2 proband. Nine patients had neurodevelopmental disorders (NDs) consisting of mild to borderline intellectual disability and/or developmental delay. There were no significant correlations between the average methylation ratios of 7 CpG sites in the GNAS-A/B:TSS-DMR and hormonal and biochemical findings. CONCLUSION: This study revealed the differences in some clinical characteristics, particularly clinical features, and ages at the time of diagnosis between G2 and other groups and detailed NDs observed in some patients with PHP1B.

Highest concentration of breast-milk-derived exosomes in colostrum.

BACKGROUND: Exosomes are nanosized extracellular vesicles, that play important roles in intercellular immune regulation. They have potential therapeutic utility for neonatal diseases including necrotizing enterocolitis. Breast-milk-derived exosomes have recently shown beneficial effects on intestinal damage in vitro and in vivo. However, the chronological change in breast-milk-derived exosome concentrations after delivery are unclear. METHODS: In this prospective study, we enrolled 17 mothers who delivered premature infants admitted to a neonatal intensive care unit in Japan. We measured the consecutive concentrations of breast-milk-derived exosomes in the mothers for 48 weeks after delivery. RESULTS: The median concentration of breast-milk-derived exosomes was 1.62 × 108 particles/ml in colostrum, showing a significant decrease after 2 weeks (P < 0.01). There was no association between the exosome concentration in colostrum and maternal perinatal factors including parity, mode of delivery, maternal age, and gestational age at delivery. CONCLUSIONS: We concluded that breast-milk-derived exosomes were the richest in colostrum. Our basic data regarding breast-milk-derived exosomes are expected to aid in the clinical application of exosomes for treating neonatal diseases.

Chronological changes of serum exosome in preterm infants: A prospective study.

BACKGROUND: Exosomes, which are observed in all human fluid, including serum, are nanosized extracellular vesicles with a mechanism of intercellular communication. Potential clinical applications of exosomes in neonatal diseases have recently been discussed. However, the characteristics of exosomes in serum during early infancy is unclear. METHODS: In this prospective study, we evaluated the chronological changes in the concentration of serum-derived exosomes of 20 infants for 12 months after birth. RESULTS: The average concentration of serum-derived exosomes was 4.6 × 1010 particles/mL at birth and increased significantly until the age of 48 weeks. There was a moderate correlation between the gestational age and the concentration of serum-derived exosomes both at birth (r = 0.54, P = 0.01) and during the 8 weeks after birth (r = 0.48, P < 0.001). A multivariable analysis showed that gestational age at birth was associated with the concentration of serum-derived exosomes at birth (partial regression coefficient, 0.86; 95% confidence interval, 0.37-1.37; P = 0.002). CONCLUSIONS: The concentration of serum-derived exosomes in preterm infants increased both chronologically and by gestational age after birth. These basic data may help to further understand physiology of exosomes in preterm infants.

Airway obstruction caused by rapid enlargement of cervical lymphangioma in a five-month-old boy.

Cervical lymphangioma can cause airway obstruction secondary to enlargement following infection. Physicians should be aware that the airway obstruction can progress rapidly when patients with cervical lymphangioma have respiratory symptoms. Sclerotherapy for lymphangioma can cause both transient swelling and airway obstruction; thus, prophylactic and elective tracheostomy should be considered.

Successful living domino liver transplantation in a child with protein C deficiency.

PC is produced in the liver and inhibits blood coagulation by catalyzing active factors V and VIII. PC deficiency causes abnormal blood clotting that is difficult to regulate by anticoagulative treatments. Four reports of PC deficiency treated with LTx have been published; however, no report of DLT as a therapy for PC deficiency is available. We describe a case of a 23-month-old girl who received DLT for compound heterozygous PC deficiency. Her PC activity was below 5%. She developed intracranial lesion and frequent refractory purpura fulminans. Both her parents had heterozygous mutations of PC genes and were excluded as living donors. Furthermore, she was a low priority on the waiting list of deceased-donor transplantation. We performed living DLT using the liver from a patient with MSUD. Activated PC concentrate safely supported the perioperative period. After DLT, she maintained normal PC activities and BCAA levels. This is the first case of PC deficiency successfully treated by living DLT with MSUD. We propose that DLT using liver from patients with MSUD is a treatment option for PC deficiency.

A case of retroperitoneal immature teratoma with nephroblastic components.

The presence of nephroblastic components is extremely rare in retroperitoneal teratomas. We described an unusual case of right retroperitoneal immature teratoma with nephroblastic components in a 2-month-old Japanese girl. Approximately 15% of tumor was composed of nephroblastic components within immature teratoma components. Although overlap of histopathological findings between teratomas with nephroblastic components and teratoid Wilms tumors, which have heterologous elements in >50% of the tumor, occasionally exist, the most distinct feature of teratoma is the presence of organoid arrangement. The prognosis of retroperitoneal teratomas with nephroblastic components has not yet been established, therefore, additional case studies are needed.

Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and varicella zoster virus encephalitis during treatment of medulloblastoma.

The case of a 14-year-old girl who developed Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and Varicella zoster virus encephalitis during treatment for medulloblastoma is described. The patient was diagnosed with a cerebral medulloblastoma and treated with systemic chemotherapy, intrathecal chemotherapy, and radiotherapy. Six months later, she developed persistent low-grade fever, abdominal pain, and vomiting. Several mucosal or ulcerated lesions of the stomach and colon were found on fiberscopy. The infiltrating cells were positive for CD20 and EBER1, and the diagnosis of lymphoproliferative disorder was made. CMV antigen was found in the peripheral lymphocytes at that time. At the same time, it was noted that the patient's language was inappropriate for her age, and a facial and abdominal rash, as well as a right facial palsy, had developed. She was then diagnosed as having VZV encephalitis, because VZV was detected in the CSF. She was treated subsequently with acyclovir and oral steroid, and the VZV encephalitis resolved. The lymphoproliferative disorder improved gradually with rituximab, ganciclovir, and total nutritional support. At the time of the development of the lymphoproliferative disorder and VZV encephalitis, the patient had severe lymphopenia and this may have caused these rare phenomena in a non-transplant setting.