Underlying diseases in sporadic presentation of high creatine kinase levels in girls.

BACKGROUND: Persistent creatine kinase (CK) elevation can occur due to various conditions. Identifying the causes of hyperCKemia is crucial for enabling appropriate follow-up and care. Girls with elevated CK levels may be carriers of Duchenne/Becker muscular dystrophy (DMD/BMD), making diagnosis more difficult than that in boys. This study aimed to elucidate the underlying causes of high CK levels in girls. METHODS: Fourteen girls (seven symptomatic, seven asymptomatic) with persistently elevated CK levels but without a family history of muscle diseases were referred to our hospital between April 2014 and August 2018. Muscle biopsy and/or genetic analysis were conducted for diagnoses. RESULTS: Among the symptomatic girls, six (85.7%) had muscular dystrophy (five DMD/BMD carriers, and one sarcoglycanopathy [limb-girdle muscular dystrophy: LGMDR4]), and one had dermatomyositis. Among the asymptomatic girls, four (57.1%) had muscular dystrophy (three DMD/BMD carriers, and one calpainopathy [LGMDR1]), and three were undiagnosed. CONCLUSION: Our results indicate that muscular dystrophy, including DMD/BMD carriers, must be considered in girls with highperCKemia regardless of symptoms presentation, and in symptomatic girls with dermatomyositis. Investigations in girls with hyperCKemia should be performed under proper ethical considerations. Further research is necessary to develop a diagnostic strategy for girls with hyperCKemia.

Late-onset ornithine transcarbamylase deficiency caused by a somatic mosaic mutation.

An 18-month-old boy was diagnosed with late-onset ornithine transcarbamylase deficiency. Genetic analysis revealed a mosaic frameshift mutation (p.Q279fs) in the OTC gene. Despite the presence of a null mutation, he exhibited a milder phenotype, suggesting that the wild-type allele could rescue the function of OTC. The presence of mosaicism has great effects on the clinical phenotype and recurrence-risk assessment, which should be taken into consideration for genetic counseling.

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Risk factors for surgical intestinal disorders in VLBW infants: Case-control study.

BACKGROUND: Very low-birthweight (VLBW) infants (VLBWI) are at increased risk for surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP) and meconium-related ileus (MRI). The aim of this study was to identify disease-specific risk factors for surgical intestinal disorders in VLBWI. METHODS: A retrospective multicenter case-control study was conducted at 11 institutes. We reviewed VLBWI who underwent laparotomy for intestinal disorders including perforation and intractable bowel obstruction. The surgical disorders were classified into four categories (NEC, FIP, MRI, others) based on the macroscopic findings at operation. In order to identify risk factors, two matched controls for each subject were chosen based on gestational age and birthweight. OR and 95%CI were calculated using a conditional logistic regression model and a multivariate model. RESULTS: A total of 150 cases (NEC, n = 44; FIP, n = 47; MRI, n = 42; others, n = 17) and 293 controls were identified. The cases and controls were similar in terms of gestational age and birthweight (cases/controls, 26.7 ± 2.5/26.5 ± 2.6 weeks; 790 ± 256/795 ± 257 g). On multivariate modeling, disease-specific risk factors were as follows: female (OR, 0.23; 95%CI: 0.06-0.89), respiratory distress syndrome (OR, 35.7; 95%CI: 2.48-514) and patent ductus arteriosus (OR, 10.9; 95%CI: 1.51-79.3) for NEC; outborn delivery (OR, 5.47; 95%CI: 1.48-20.2) for FIP; and twin pregnancy (OR, 4.25; 95%CI: 1.06-17.1), PROM (OR, 6.85; 95%CI: 1.33-35.4) and maternal steroid (OR, 0.23; 95%CI: 0.07-0.79) for MRI. CONCLUSIONS: Different risk factors were identified for NEC, FIP and MRI, suggesting that each disease has a different etiology, and that different strategies are required to prevent these diseases.

Hyperinsulinemic hypoglycemia of infancy in Sotos syndrome.

Sotos syndrome (OMIM #117550) is a congenital syndrome characterized by overgrowth with advanced bone age, macrocephaly, and learning difficulties. Endocrine complications of this syndrome have not yet been fully described in previous reports. We here investigated the clinical manifestations of Sotos syndrome in Japanese patients who presented with hyperinsulinemic hypoglycemia of infancy. We recruited patients diagnosed as having Sotos syndrome who presented with the complication of hyperinsulinemia during the neonatal period using a survey of the abstracts of Pediatric Meetings in domestic areas of Japan from 2007 to 2011. As a result, five patients (four females and one male) were recruited to evaluate the clinical presentation of Sotos syndrome by reference to the clinical record of each patient. A 5q35 deletion including the NSD1 gene was detected in all patients. Major anomalies in the central nervous, cardiovascular, and genito-urinary systems were frequently found. Hypoglycemia occurred between 0.5 and 3 hr after birth and high levels of insulin were initially found within 3 days of birth. The patients were treated with intravenous glucose infusion at a maximum rate of 4.6-11.0 mg/kg/min for 12-49 days. Three of the five patients required nasal tube feeding. One patient received medical treatment with diazoxide. This study shows that patients with Sotos syndrome may present with transient hyperinsulinemic hypoglycemia in the neonatal period.