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THE JOURNAL OF THE JAPAN PEDIATRIC SOCIETY

Vol.124, No.5, May 2020


Original Article
1. Circadian Rhythm at Age 3-4 Months is Associated With Risk of Autism Spectrum Disorder
2. Effectiveness of Antibiotic Therapy Guided by Culture Results for Staphylococcal Scalded Skin Syndrome
Case Report
1. A Case of Massive Pulmonary Hemorrhage from Dual Circulation Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
2. Chronic Granulomatosis Disease Complicated with Macrophage Activation Syndrome Related to Rifampicin Administration
3. Postnatal Failure to Thrive, Overeating, and Developmental Delay with KIAA2022 Mutation: A Case Report
4. Centrifugal Leukocytapheresis for Pediatric Acute Myeloid Leukemia Presenting with Leukocytosis
5. Holocarboxylase Synthetase Deficiency Treated with Strict Dietary Management due to Incomplete Biotin Responsiveness


Original Article
Title
Circadian Rhythm at Age 3-4 Months is Associated With Risk of Autism Spectrum Disorder
Author
Kyoko Hoshino1) Yuri Nagao1) Kazue Kimura1) Masaharu Hayashi1) and Yosuke Kita2)
1)Segawa Memorial Neurological Clinic for Children
2)Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry
Abstract
Background
We analyzed the association of sleep awakening rhythm at age 3-4 months with the risk of autism spectrum disorder (ASD).
Objectives and Methods
Data were collected from 52 patients at our neurological clinic, namely, consolidation of circadian rhythm at age 3-4 months (Q1), frequent night crying (Q2), good circadian at age 1 year (Q3), and good circadian in early childhood (Q4). All information was collected retrospectively from medical records.
Results
Of patients, 65% answered affirmatively to Q1, 82% reported no crying during the night (Q2), and 88% and 76% reported good circadian rhythm for Q3 and Q4, respectively. These proportions were significantly higher than those for patients who answered negatively to Q1 (p<0.05). Of patients, 61% answered negatively to Q1 later diagnosed with ASD. Further analysis of risk factors for subsequent ASD development revealed that patients who answered negatively to Q1, affirmatively to Q2, and negatively to Q3 had a significantly higher risk of ASD.
Discussion
Irregular circadian rhythm at age 3-4 months is associated with an increased risk of subsequent ASD (approved by the Segawa Memorial Neurological Clinic for Children Ethics Committee; No 18-01).




Original Article
Title
Effectiveness of Antibiotic Therapy Guided by Culture Results for Staphylococcal Scalded Skin Syndrome
Author
Aiko Honda1)2) Eiki Ogawa3) Kensuke Shoji3) Mitsuru Kubota2) Akira Ishiguro1) and Isao Miyairi3)
1)Center for Postgraduate Education and Training, National Center for Child Health and Development
2)Division of General Pediatrics, Department of Interdisciplinary Medicine, National Center for Child Health and Development
3)Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development
Abstract
Staphylococcal scalded skin syndrome (SSSS) is a disease occurring in early childhood, which presents with desquamation caused by an exfoliative toxin produced by Staphylococcus aureus. Antibiotics therapy guided by culture is performed for patients with SSSS, although the usefulness of this strategy is unknown. Patients who were admitted with a diagnosis and symptoms compatible with SSSS and had S. aureus isolated from clinical specimens, from November 2006 to January 2018, served as our patient population. Patients who received antibiotics that confer susceptibility to the isolate, for 5 days or more, were defined as the matched susceptibility group. Thirty-four cases were included, and the median age was 17 months. Erythema, Nikolsky sign, and purulent discharge of the eye were found in 97%, 91%, and 53% of cases, respectively. S. aureus was detected in 34 cases, including 22 cases with methicillin-resistant S. aureus. Antibiotics were administered in all cases. There were no significant differences regarding clinical course between sensitivity matched (n=17) and unmatched groups (n=17), symptomatic period (6 vs. 5 days, p=0.27), and hospitalization days (7 vs. 7 days, p=0.43). Antibiotic therapy, guided by culture results, may not shorten the symptomatic period and hospital stay for patients with SSSS.




Case Report
Title
A Case of Massive Pulmonary Hemorrhage from Dual Circulation Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Author
Toshikatsu Tanaka1) Kazuya Uemura2) Yasunobu Miki1) Michio Matsuoka1) Naoya Kamei1) Yasuharu Ogawa1) Kenta Tominaga1) and Sachiko Kido1)
1)Department of Cardiology, Hyogo Prefectural Kobe Children's Hospital
2)Department of Pediatrics, Kakogawa Central City Hospital
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of multiple arteriovenous malformations involving the lungs, liver, brain, and spinal cord. Pulmonary arteriovenous malformation (PAVM) may lead to life-threatening hemoptysis and a right-to-left shunt causing paradoxical embolism, with consequent stroke or cerebral abscess.
We report a case of a 15-year-old male adolescent with multiple PAVMs associated with HHT. He developed recurrent massive pulmonary hemorrhage from dual circulation PAVM, which received blood supply from both the pulmonary and systemic circulation. In the first session, we performed coil embolization from the pulmonary artery; however, this procedure was ineffective. In the second session, we performed aortic angiography, which revealed collateral arterial supply to the right lung, and additional coil embolization from the aortic aspect. Recurrent episodes of massive hemoptysis necessitated lung resection.
Clinicians should be aware that PAVMs are associated with dual circulation; therefore, aortic angiography is indicated in patients who develop recurrent hemoptysis after coil embolization of the pulmonary artery. Prompt conversion to lung resection is warranted in patients in whom coil embolization is ineffective.




Case Report
Title
Chronic Granulomatosis Disease Complicated with Macrophage Activation Syndrome Related to Rifampicin Administration
Author
Tomoko Ohara1) Kentaro Miyai1) Kay Tanita2) Chika Hiraishi1) Kio Fukuyama1) Eiichiro Tamura3) Toshinao Kawai3) Kohsuke Imai2) Hirokazu Kanegane2) and Koji Kiyohara1)
1)Department of Pediatrics, Tokyo-Kita Medical Center
2)Department of Pediatrics, Tokyo Medical and Dental University
3)Division of Immunology, National Center for Child Health and Development
Abstract
Chronic granulomatous disease (CGD) is a phagocytic disorder caused by a defect in the nicotinamide adenine dinucleotide oxidase complex, and it is characterized by recurrent infections and hyperinflammation since infancy. Macrophage activation syndrome (MAS) is a life-threatening complication of excessive immune activation in rheumatic disease and characterized as persisting activation of macrophage by cytokine storms. To date, there were some reports regarding patients with CGD associated with MAS, and all of them were due to some microbial infections except two reports with unknown etiology. Here, we report a case of CGD complicated with MAS related to rifampicin administration. A 1-year-old boy was admitted for treatment of pneumonia. He had a refractory perianal abscess and inguinal lymphadenitis. He was also suspected of having Bacillus Calmette-Guérin (BCG) infections. Flow cytometric and genetic analyses disclosed X-linked CGD. Although pneumonia was improved by treatment with multiple antibiotics, he showed fever again after the administration of antituberculosis drugs for BCG infection. Laboratory tests showed hyperferritinemia, elevated aminotransferase, elevated triglyceride, and hypofibrinogenemia; thus, he was diagnosed as having MAS. In this report, we discuss the causal mechanisms of the MAS in the present case.




Case Report
Title
Postnatal Failure to Thrive, Overeating, and Developmental Delay with KIAA2022 Mutation: A Case Report
Author
Yuuki Hashimoto1) Yukako Muramatsu1)2)3) Ayako Yasuda1) Tomoko Uehara4) Kenjiro Kosaki4) and Makoto Ooshiro1)
1)Department of Neonatology, Japanese Red Cross Nagoya Daiichi Hospital
2)Department of Pediatrics, Nagoya University Hospital
3)Department of Clinical Genetics, Central Hospital, Aichi Developmental Disability Center
4)Center for Medical Genetics, Keio University School of Medicine
Abstract
KIAA2022 abnormality is one of the X-linked intellectual disabilities. We report a 5-year-old boy presenting with a growth disorder and delayed development, in which a frame-shift mutation [c.3530delA, p. (Lys1177Argfs*11)] was identified in KIAA2022 through whole-exome sequencing.
No problems were observed during his mother's pregnancy, and the patient was born with a physique typical of a full-term infant (height = 0.3 SD, body weight = −1.0 SD). The postnatal growth disorder progressed, with his height being −4.7 SD and body weight −2.2 SD (5 years). Overall, the development was slow, and he could pull himself up but could not walk at the age of 5 years. Although he could not speak meaningful words, he could communicate with simple gestures. He showed interest in other people and displayed no signs of autistic behavioral tendencies. Overeating, repeated emesis after meals, and transient hypothyroidism were observed.
It is difficult to recognize KIAA2022 abnormality from its previously reported nonspecific clinical symptoms and facial features. Whole exome sequencing is very useful in an examination of intellectual disorder of unknown cause, to lead to accurate diagnosis and evidence-based genetic counseling.
Further accumulation of case data is required.




Case Report
Title
Centrifugal Leukocytapheresis for Pediatric Acute Myeloid Leukemia Presenting with Leukocytosis
Author
Hideki Ban1)2) Shota Fujito1) Mariko Nagayoshi1) Satomi Yokoyama1) Naoki Yogo1) Katsuki Hirai1) Masahiro Migita1) Kazunari Torigoe3) Megumi Eguchi3) Norio Hanafusa4) Kenichiro Miura2) and Motoshi Hattori2)
1)Department of Pediatrics, Japanese Red Cross Kumamoto Hospital
2)Department of Pediatric Nephrology, Tokyo Women's Medical University
3)Department of Clinical Engineering, Department of Nephrology, Japanese Red Cross Kumamoto Hospital
4)Department of Blood Purification, Kidney Center, Tokyo Women's Medical University
Abstract
Leukocytosis caused by leukemia is an oncological emergency associated with a high risk of life-threatening complications, including cerebral infarction, pulmonary infarction, tumor lysis syndrome, acute kidney injury, and disseminated intravascular coagulation. A 10-year-old girl with marked leukocytosis of up to 263,340/μL (blast 96%) was diagnosed with acute myeloid leukemia on bone marrow examination. Since hypoxemia, headache, and swelling and pain in the bilateral lower extremities were observed as symptoms of leukocytosis, leukocytapheresis was performed twice through centrifugation. In both treatments, the processed blood volume was four fold the total blood volume, and the leukocyte count was reduced by 71% and 75% on the first and second treatments, respectively. Leukocytosis symptoms improved during treatment with a reduction in the leukocyte count. Centrifugal leukocytapheresis for leukocytosis caused by pediatric acute myeloid leukemia is an effective treatment method to safely eliminate excessive leukocytes and improve symptoms.




Case Report
Title
Holocarboxylase Synthetase Deficiency Treated with Strict Dietary Management due to Incomplete Biotin Responsiveness
Author
Kenji Ichinomiya1) Kenichi Maruyama1) Aya Koizumi1) Kazuyo Fukuda1) Yu Yamazaki1) Kota Kaburagi1) Yoichi Miyakawa1) Yu Yamaguchi2) Sayaka Ajihara3) Akira Ohtake3) and Mitsuru Kubota4)
1)Departments of Neonatology, Gunma Children's Medical Center
2)Division of Genetics, Gunma Children's Medical Center
3)Department of Pediatrics, Faculty of Medicine, Saitama Medical University
4)Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development
Abstract
A male neonate, weighing 2,240 g, was delivered on the 37th week of gestation and transferred to our hospital on day 7 because of metabolic acidosis. The results of tandem mass spectroscopy-showing elevated levels of propionylcarnitine and 3-hydroxyisovalerylcarnitine-combined with the urine analysis results revealed the presence of organic acids in a complex pattern, suggesting a case of holocarboxylase synthetase deficiency (HCSD). Additionally, HLCS analysis revealed a compound heterozygous mutation (p.Leu237Pro/p.Gly261fs), confirming HCSD. Despite having received a high dosage of biotin upon admission, he developed marked hyperammonemia, therefore requiring hemodialysis. Once the metabolic crisis was resolved, there was an onset of acute metabolic decompensation due to increased enteral nutrition. Therefore, a diet low in protein and rich in fat was used to manage the condition, resulting in improved clinical and biochemical findings. Episodes of metabolic decompensation ceased, and strict dietary management was discontinued at 11 months of age.
Clinical responses to biotin therapy differ between haplotypes. We should be aware that patients with a mutation in HLCS accompanied by incomplete biotin responsiveness may require strict dietary management.




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