gakkaizashi


THE JOURNAL OF THE JAPAN PEDIATRIC SOCIETY

Vol.125, No.8, August 2021


Original Article
1. Clinical Characteristics of Neonatal Adrenal Hemorrhage in 78 Patients Reported Nationwide and an Infant Delivered at Our Institution
2. Prevalence of Vitamin D Deficiency in Children with Food Allergy
3. Comparison of Serotypes of Pneumococci Isolated in 2108 from the Nasopharynx of Young Children between Two Distant Areas in Japan
4. Patient Distribution of Brief Resolved Unexplained Event Classification for Apparent Life-threatening Events
Case Report
1. Prepubertal Case of Deep Venous Thrombosis during Purulent Hip Arthritis Treatment
2. An Infant with Toxic Shock Syndrome and Acute Encephalopathy Caused by Minor Burn Injury
3. Megaloblastic Anemia Due to Unbalanced Diet and Poor Adherence
4. Pork-cat Syndrome Repeating Gastrointestinal Symptoms Triggered by Pork or Beef Since Three Years Old: A Case Report
5. Diagnosis of Alazami Syndrome Based on Whole Exome Sequencing in a Boy with Short Stature and Psychomotor Developmental Disability
6. Congenital Hypothyroidism with Falsely Elevated TRAb Due to the Use of Lithium Heparin-containing Micro Tubes
7. A Case of COVID-19 in the Family but with no Transmission from Children to Mother
8. Interferon-mediated Autoinflammatory Disease Which Took 16 Years to Accurately Diagnose
Brief Report
Antibody Prevalence against SARS-CoV-2 among Children Visiting a Children's Hospital


Original Article
Title
Clinical Characteristics of Neonatal Adrenal Hemorrhage in 78 Patients Reported Nationwide and an Infant Delivered at Our Institution
Author
Takahiro Noda1) Yoshiyuki Sakai1) Yoshimasa Kudo1) Satoshi Nakamura1) Tomohiro Wakabayashi1) Yuhei Kawashima1) and Yukihiko Kawasaki2)
1)Department of Pediatrics, Hakodate Municipal Hospital
2)Department of Pediatrics, School of Medicine, Sapporo Medical University
Abstract
The clinical manifestations of neonatal adrenal hemorrhage in newborns are poorly documented in Japan. Neonatal adrenal hemorrhage can be asymptomatic but can result in shock and, consequently, death. The risk factors for neonatal adrenal hemorrhage include vacuum extraction, forceps delivery, and heavy-for-date infants. We reviewed domestic case reports of 79 patients with neonatal adrenal hemorrhage. About half of the babies were born as heavy-for-date; such infants were more likely to experience mechanical compression of adrenal glands during vaginal delivery. This indicates neonatal adrenal hemorrhage as being one of the injuries associated with vaginal delivery. Moreover, given the number of patients requiring exchange and other blood transfusions, as well as fatal cases, early diagnosis of neonatal adrenal hemorrhage remains clinically significant. In this report, we outlined the clinical presentations of neonatal adrenal hemorrhage, and provided a clinical course for an asymptomatic male baby subject.




Original Article
Title
Prevalence of Vitamin D Deficiency in Children with Food Allergy
Author
Junko Oikawa1)3) Shuji Sai1) Anna Ohtani1) Kiyoshi Nagumo1) Akemi Sugihara2) and Akiko Tamakoshi3)
1)Department of Pediatrics, Teine-Keijinkai Hospital
2)Sugihara Pediatrics & Allergy Clinic
3)Department of Public Health, Hokkaido University Graduate School of Medicine
Abstract
[Background]: We performed this study to clarify the prevalence of vitamin D deficiency in children with food allergies living in northern Japan.
[Methods]: We studied patients under 3 years of age with a chief complaint of food allergies, who were seen at our hospital in Sapporo during a 2-year period, from April 2017. We obtained information about food and lifestyle from the questionnaire that was filled out by a guardian and assessed the condition of vitamin D deficiency through blood tests.
[Results]: Of the 71 subjects, 48 (67.6%) subjects had lower levels of 25(OH)D, less than 20 ng/mL. In the vitamin D-deficient group, the rate of breast-fed infants was significantly higher (p < 0.01). One subject was diagnosed with rickets caused by vitamin D deficiency. We analyzed the results, excluding the one case of rickets, and found that the intact PTH levels were still significantly higher in the vitamin D-deficient group (p < 0.01). There was no correlation between dietary restrictions and 25(OH)D deficiency. More than half of the children were deficient in vitamin D through all seasons.
[Conclusion]: We recommend vitamin D supplementation to all infants throughout the year, as children living in northern Japan are likely to be deficient in vitamin D even without restricted foods.




Original Article
Title
Comparison of Serotypes of Pneumococci Isolated in 2108 from the Nasopharynx of Young Children between Two Distant Areas in Japan
Author
Akiyoshi Nariai1)3) Takanori Yanai2) Tomohiro Hirade3) Akiyoshi Horie3)4) and Takashi Nishizawa5)
1)Department of Infectious Diseases, Matsue Red Cross Hospital
2)Department of Pediatrics, National Hospital Organization Yokohama Medical Center
3)Department of Pediatrics, Shimane Central Prefectural Hospital
4)Department of Pediatrics, Matsue Red Cross Hospital
5)Department of Pediatrics, Yokohama Minami Kyosai Hospital
Abstract
Nasopharynx (NP) colonization is the first step in disease pathogenesis of Streptococcus pneumoniae. We began carriage surveillance of S. pneumoniae among children with lower respiratory infections, younger than 6 years of age, at a general hospital in Kanazawa ward in 2010. Since then we have monitored serotypes of S. pneumoniae isolated from NP of young children. In 2018, we had an opportunity to investigate serotypes of S. pneumoniae with the same methods in Izumo city. We compared characteristics of serotypes of S. pneumoniae obtained in 2018 between these two distant areas.
NP swabs from 323 and 415 children (median age of 1 year) were obtained respectively. A total of 66 and 108 isolates of S. pneumoniae were obtained respectively; twenty percent and 26% of children were colonized with S. pneumoniae, respectively.
Isolates were serotyped using Quellung reaction. The numbers of identified serotypes were 22 and 18, respectively. In the 13-valent pneumococcal conjugate vaccine (PCV13), 100% and 97% were not serotypes, respectively. In Izumo city, serotype 3 was isolated from three children. Fourteen serotypes were identical in two areas, which accounted for 64% of identified serotypes in Kanazawa ward and 78% in Izumo city. In Kanazawa ward, 11A/E and 35B were the most common serotypes (10.8%, respectively). In contrast, 23A was most common in Izumo city (19.4%).
Our data suggests that PCV13 serotypes have almost been eliminated 5 years after PCV13 introduction, but there were some different characteristics in the distribution of non-PCV13 serotypes among different areas.




Original Article
Title
Patient Distribution of Brief Resolved Unexplained Event Classification for Apparent Life-threatening Events
Author
Daiki Tanaka1) Shunsuke Amagasa1) Nanae Kikuchi2) Ryuji Sasaki1) Satoko Uematsu1) Satoshi Tsuji1) Mitsuru Kubota3) and Satoshi Nakagawa2)4)
1)Division of Pediatric Emergency and Transport Services, National Center for Child Health and Development
2)Center for Postgraduate Education and Training, National Center for Child Health and Development
3)Division of General Pediatrics & Interdisciplinary Medicine, National Center for Child Health and Development
4)Department of Critical Care Medicine, National Center for Child Health and Development
Abstract
BACKGROUND
In 2016, brief resolved unexplained events (BRUE) and their risk classification were proposed as an alternative to the concept of apparent life-threatening events (ALTE). As a pilot study to examine the usefulness of managing ALTE cases by BRUE-based classification in Japan, we report cases at our hospital that have occurred within a year.
METHODS
From January to December 2019, we conducted a retrospective study of ALTE on patients aged <1 year at the Emergency Department. Patients were classified according to whether they corresponded to higher-risk or lower-risk BRUE. Other patients were classified as ALTE not BRUE, which consisted of ALTE that did not correspond to BRUE.
RESULTS
Eleven cases were included, of which four cases were ALTE not BRUE; three were higher-risk BRUE; and four cases were lower-risk BRUE. One case of ALTE not BRUE and one case of higher-risk BRUE were diagnosed with subdural hematoma and breath-holding spell, respectively.
CONCLUSION
In some cases, complete replacement of ALTE with BRUE is difficult, and their definitions do not overlap.




Case Report
Title
Prepubertal Case of Deep Venous Thrombosis during Purulent Hip Arthritis Treatment
Author
Ayako Miyazawa1) Yuichi Ogawa1) Kotaro Araki2) and Hiroshi Hataya1)
1)Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center
2)Division of Infection Disease, Tokyo Metropolitan Children's Medical Center
Abstract
Although venous thromboembolisms (VTE) are much less common in children than in adults, the incidence in children has increased during the past decade. Evidence-based guidelines for VTE risk assessment and prophylaxis are well established for adults but not for children due to a paucity of evidence.
We report the case of a 10-year-old male patient in whom deep venous thrombosis (DVT) developed during treatment of purulent hip arthritis. The thrombus extended from the knee socket to the common iliac vein. He had no inherited risk factors but had other risks, such as infection, obesity, and immobility. The DVT risk was underestimated in the present study due to the patient's prepubertal age despite the presence of certain risk factors.
Potential complications of DVT include pulmonary embolisms (PE) and post-thrombotic syndrome (PTS), which is the most frequent long-term complication. Symptoms of PTS, including pain, cramps, swelling, and itching, worsen the QOL of affected children. While DVT occurs at its peak after puberty, to enable early detection and treatment, its risk should not be overlooked even in prepubertal patients.




Case Report
Title
An Infant with Toxic Shock Syndrome and Acute Encephalopathy Caused by Minor Burn Injury
Author
Haruka Takami1) Norimichi Higurashi1) Yuriko Sekiguchi1) Ken Ito1) and Naoto Takahashi2)
1)Department of Pediatrics, Jikei University School of Medicine
2)Department of Pediatric and Neonatal Intensive Care, The University of Tokyo Hospital
Abstract
Toxic shock syndrome (TSS) is associated with burn injury. Case reports of both TSS and acute encephalopathy are rare. We encountered an 11-month-old boy who developed both TSS and acute encephalopathy after minor burns. Five days prior to admission, he suffered 10% burns on the neck and forearm. He was examined by a general pediatrician and did not undergo special care for the burned skin. The day before admission, the patient developed fever and a convulsion. Despite acute treatment at a previous hospital, the seizure lasted for 3 hours followed by severe hypotension. He was transferred to the intensive care unit at our hospital. He presented with multiple organ failure. Serum and cerebrospinal fluid cytokine levels were significantly increased at the time of admission. Although no skin rash was identified on admission, the results of blood and cerebrospinal fluid cultures were negative, MRSA and TSST-1 were identified from the burn site, and peripheral desquamation appeared in the third week of hospitalization, resulting in a diagnosis of TSS. Diffuse high voltage slow waves on electroencephalogram, diffuse white matter lesions followed by a cerebral atrophy on brain MRI, and other clinical features further indicated diagnosis of acute encephalopathy. It is crucial to carefully follow up children with mild burns for such severe complications.




Case Report
Title
Megaloblastic Anemia Due to Unbalanced Diet and Poor Adherence
Author
Yasuyuki Fuseda1)2) Kyohei Isshiki1) Tomoo Osumi1) Akira Ishiguro2) Reiko Horikawa3) Kimikazu Matsumoto1) Daisuke Tomizawa1) and Motohiro Kato1)
1)Children's Cancer Center, National Center for Child Health and Development
2)Center for Postgraduate Education and Training, National Center for Child Health and Development
3)Division of Endocrinology and Metabolism, National Center for Child Health and Development
Abstract
A 9-year-old boy with autism spectrum disorder and vitamin D deficiency rickets was referred to our hospital due to pancytopenia and failure to thrive. Medical history revealed significant unbalanced diet and excessive food selectivity. There was poor adherence to taking prescribed vitamin supplements. Bone marrow aspiration showed megaloblastic changes without any leukemic blasts. Megaloblastic anemia was diagnosed based on low serum values of folic acid and vitamin B12. The pancytopenia resolved promptly with intravenous vitamin supplementation. We offered nutritional guidance and urged improved adherence to prescriptions because vitamin D deficiency rickets was also affected by poor adherence.
Food selectivity is a common and chronic problem in autism spectrum disorder and may lead to vitamin deficiency. More attention must be paid to adherence, even when a child with autism spectrum disorder has a prescription for vitamins. We should conduct medical examinations and interviews considering megaloblastic anemia as one of the causes of pancytopenia.




Case Report
Title
Pork-cat Syndrome Repeating Gastrointestinal Symptoms Triggered by Pork or Beef Since Three Years Old: A Case Report
Author
Eriko Kudo1) Shunichiro Takezaki2) Takeshi Yamazaki1) Tomoshiro Ito1) Kinya Hatakeyama1) Nobuaki Kawamura1) and Hitomi Sano1)
1)Department of Pediatrics, Sapporo City General Hospital
2)Department of Pediatrics, Hokkaido University Hospital
Abstract
Pork-cat syndrome (PCS) is a disorder presenting allergic-reactions to pork products by means of cross-reactivity after primary sensitization to feline serum albumin. Here, we report a 6-year-old boy with PCS who repeated gastrointestinal symptoms soon after eating pork or beef since three years old. He had cats in his house. Allergen-specific IgE testing showed positive results for both feline and porcine serum albumin. The skin prick test revealed positive reactions to raw meats (pork, beef and lamb) and negative reactions to cooked meats. He was diagnosed with PCS by present history, blood test and skin prick test. This is the youngest case of PCS among previously published childhood-onset cases. Since patients with PCS usually tolerate well-cooked meat, it is important to consider PCS when treating patients with meat allergy.




Case Report
Title
Diagnosis of Alazami Syndrome Based on Whole Exome Sequencing in a Boy with Short Stature and Psychomotor Developmental Disability
Author
Kasumi Sasaki1) Nobutsune Ishikawa1) Hiroko Shimoda2) Hiromi Fukuda3) Takeshi Mizuguchi3) Naomichi Matsumoto3) and Satoshi Okada1)
1)Department of Pediatrics, Hiroshima University Hospital
2)Department of Pediatrics, National Hospital Organization Higashihiroshima Medical Center
3)Department of Human Genetics, Yokohama City University Graduate School of Medicine
Abstract
Alazami syndrome is an autosomal recessive disorder caused by biallelic pathogenic variants in the La ribonucleoprotein domain family member 7 gene (LARP7). The patients develop severe growth restriction, psychomotor developmental disability, and distinct facial features. To date, only 26 patients from 13 families have been reported. Here, we describe a boy with short stature and psychomotor developmental disability who was diagnosed with Alazami syndrome, whose whole exome sequencing detected a novel compound heterozygous variant in LARP7. We summarize previous reviews and this case and contribute to the delineation of the phenotypic spectrum of Alazami syndrome.




Case Report
Title
Congenital Hypothyroidism with Falsely Elevated TRAb Due to the Use of Lithium Heparin-containing Micro Tubes
Author
Shota Hiroshima1) Masako Hayashi1) Kentaro Sawano1) Hiromi Nyuzuki1) Yohei Ogawa2) and Keisuke Nagasaki1)
1)Department of Pediatrics, Niigata University Medical & Dental Hospital
2)Department of Community Medicine, Niigata University Graduate School of Medical and Dental Sciences
Abstract
Endocrine tests use antigen-antibody reactions as the measurement principle. Non-specific reactions should be suspected when discrepancies exist between the clinical picture and clinical test results. We report the case of a girl with 4p- syndrome who was suspected to have the possibility of non-specific reactions in thyroid-related tests during levothyroxine Na (LT4) replacement for severe congenital hypothyroidism (CH). On day 15 of life, her TSH and FT4 were 2,467 μIU/mL and 0.20 ng/dL, respectively. She was diagnosed with severe CH and started on replacement with 10 μg/kg/day of LT4. Her TSH receptor antibody (TRAb, third generation) remained weakly positive at the initial diagnosis, but maternal TRAb was negative. Although FT4 levels increased above the normal range with increasing LT4 dosage, TSH levels did not normalize. Both TSH and TRAb levels were suspected of false elevation due to non-specific reactions.
The TSH dilution linearity was confirmed. Serum TRAb was negative for serum separation tube use. Lithium-heparin plasma samples were used during NICU blood sampling. TSH levels were normalized by increasing LT4. TRAb levels were higher in the lithium heparin-containing tubes than in the serum. Physicians should be aware that third-generation TRAb in lithium heparin-containing tubes can produce false high results.




Case Report
Title
A Case of COVID-19 in the Family but with no Transmission from Children to Mother
Author
Ken Sugata1) Katsumi Sugiura1) Mizuho Nagao1) Toshihiko Shinoki1) Shigeru Suga1) Kiyosu Taniguchi1) Hidenori Ibata2) and Takao Fujisawa1)
1)Department of Pediatrics, National Hospital Organization, Mie National Hospital
2)Department of Respiratory Medicine, National Hospital Organization, Mie Chuo Medical Center
Abstract
In this study, we report the epidemiological and microbiological findings of two children (daughters) in a family cluster who were infected with SARS-CoV-2 from their father, but the mother was negative by PCR test even though she had been in the same room with the daughters for two weeks.
Although, the children had underlying medical conditions; one with trisomy 21 and the other with food allergies and history of anaphylaxis, the symptoms of COVID-19 infection were minor and only required observation without treatment.
In the serial PCR test results, the SARS-CoV-2 viral load of both patients decreased rapidly, but tended to be prolonged in the one with trisomy 21.
There have been many reports of intrafamilial transmission of SARS-CoV-2 from an adult to a child. However, the transmission risk from a child to an adult seem to be relatively lower. Further investigation is imperative in order to better understand the transmission dynamics of SARS-CoV-2 from a child to an adult.




Case Report
Title
Interferon-mediated Autoinflammatory Disease Which Took 16 Years to Accurately Diagnose
Author
Yoshikazu Otsubo Keiko Hashimoto and Akira Kamitamari
Department of Pediatrics, Sasebo City General Hospital
Abstract
Although the Type I interferon (IFN) response is a normal immune response to viral infections, its abnormal activation may cause a serious Mendelian inheritance disorder called type I interferonopathy. The patient was a 16-year-old girl. She developed a chilblain-like rash at 3 months of age and thereafter suffered from repeated fever and erythema nodusum. A skin biopsy at 7 months of age revealed panniculitis and she was diagnosed with Weber-Christian disease. Despite initiating oral prednisolone at 2 years of age, systemic symptoms, such as uveitis, knee arthritis, and remittent fever were observed. Autoantibodies were negative and no gene mutations associated with autoinflammatory disease were found. Immunosuppressants and biologics (anti-TNF-α agent, anti-IL-6 agent) were sequentially introduced since 5 years old of age, enabling the suppression of joint and ocular symptoms. However, a self-limited fever and erythema nodosum persisted, with CRP remaining positive. At 16 years of age, she showed calcification of both basal ganglia on head CT and an elevated IFN signature. A PSMB8 gene mutation associated with Nakajo-Nishimura syndrome was negative, and no significant mutations were found according to a whole exome analysis. However, in addition to specific clinical features, calcification of the basal ganglia and an increased IFN signature were observed, thus resulting in a clinical diagnosis of IFN-mediated autoinflammatory disease. Both examinations are useful tools in early diagnosis.




Brief Report
Title
Antibody Prevalence against SARS-CoV-2 among Children Visiting a Children's Hospital
Author
Takuma Ohnishi1) Yumi Toda2) Hiroyoshi Imura2) and Satoshi Sato1)
1)Division of Infectious Diseases and Immunology, Saitama Children's Medical Center
2)Department of Clinical Laboratory, Saitama Children's Medical Center
Abstract
In Japan, the prevalence of coronavirus disease 2019 (COVID-19) in the general population has been estimated by measuring antibody titers; however, its prevalence in children has not been investigated. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers of 500 pediatric patients were analyzed randomly from residual samples at the Saitama Children's Medical Center in September 2020. There were four positive cases (0.8%); one patient was positive for immunoglobulin G, and the other three were positive for immunoglobulin M. Because most children lacked the SARS-CoV-2 antibodies, there was a danger of COVID-19 spreading further. It is necessary to continue taking sufficient measures to prevent infection, even in general outpatient settings.




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