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THE JOURNAL OF THE JAPAN PEDIATRIC SOCIETY
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Vol.120, No.10, October 2016
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Original Article
Title
Newborn Screening for Severe Combined Immunodeficiency Using T-cell Receptor Excision Circles
Author
Daiei Kojima1) Yuichiro Sugiyama2) Hideki Muramatsu1) Daiki Kondo2) Masahiro Yasui3) Shinji Kido3) Yoshiaki Sato2) Masahiro Hayakawa2) and Seiji Kojima1)
1)Department of Pediatrics, Nagoya University Graduate School of Medicine
2)Division of Neonatology, Center for Maternal-Neonatal Care Nagoya University Hospital
3)Department of Pediatrics, Nakatsugawa Municipal General Hospital
Abstract
Background: Global progress has been made in newborn screening (NBS) for severe combined immunodeficiency (SCID). We measured T-cell receptor excision circles (TREC), a marker of T lymphopoiesis, to evaluate whether it would be suitable for NBS in Japan. Objective and Methods: We studied 213 neonates born in Nagoya University and Nakatsugawa Municipal General Hospital during 2015 by examining 9 stored mononuclear cell samples from patients diagnosed with SCID (IL2RG, n=1; RAG1, n=2; LIG4, n=1; AK2, n=1; JAK3, n=1), late onset combined immunodeficiency (IL2RG, n=1; RAG1, n=1; causative gene unknown, n=1), and 18 stored samples from age-matched healthy children. Results: The median TREC copy number of the newborns was 139 (range 32-473) copies/μL, which was higher than the cut-off value of 29 copies/μL. With regards to stored samples, the median TREC copy number of SCID patients was 4 (range 3-8) copies/μL and that of healthy children was 455.5 (range 44-473) copies/μL. Conclusion: This study demonstrated that TREC quantification is a suitable screening test for SCID in Japan. This screening test should be introduced to our country.
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Original Article
Title
Sensitivity and Specificity of the Systemic Lupus International Collaborating Clinics Classification Criteria for Childhood-onset Systemic Lupus Erythematosus
Author
Mayuka Shiraki1) Shiro Sugiura2) Haruna Nakaseko1) Shinji Kawabe1) and Naomi Iwata1)
1)Departments of Infection and Immunity, Aichi Children's Health and Medical Center
2)Departments of Allergy, Aichi Children's Health and Medical Center
Abstract
For the diagnosis of systemic lupus erythematosus (SLE), the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria (2012) were proposed in addition to the American College of Rheumatology (ACR) classification criteria (1997) for adults. In Japan, the diagnostic criteria developed in 1985 by the Pediatric Study Group of the Japanese Ministry of Health and Welfare (JMHW) were used to diagnose SLE in children and adolescents, and these include 11 criteria established by the ACR (1982) and hypocomplementemia. The SLICC criteria had greater sensitivity but lower specificity than the ACR criteria for adults. We aimed to compare the sensitivity and specificity of the SLICC criteria with those of the ACR and JMHW criteria for childhood-onset SLE patients. We included 51 children and adolescents with SLE, and 37 children and adolescents with other rheumatic diseases (juvenile dermatomyositis, mixed connective tissue disease, primary Sjogren syndrome), as controls, who were admitted in our hospital. The sensitivity of the ACR, JMHW, SLICC criteria were 76%, 94%, and 100%, respectively. Their specificity were 100%, 96.4%, and 89.2%, respectively. In our population, the SLICC criteria also showed better sensitivity but lower specificity than the ACR criteria. It is necessary to pay attention to other possible rheumatic diseases as differential diagnoses when using the SLICC criteria in the diagnosis of SLE.
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Case Report
Title
Anterior Basal Meningoencephalocele in Neonate: Report of Three Cases
Author
Shuhei Fujino Shoichiro Amari Masao Kaneshige Fumiko Miyahara Ikuko Hama Yuka Wada Shigehiro Takahashi Hideshi Fujinaga Keiji Goishi Keiko Tsukamoto and Yushi Ito
Division of Neonatology, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development
Abstract
Introduction: Meningoencephalocele is a congenital anomaly characterized by protrusion of part of the brain through a defect in the skull. Meningoencephalocele rarely occurs in the anterior cranial base, with a frequency of one in 35,000-40,000 live births at risk of respiratory obstruction and meningitis. We report three rare cases of anterior basal meningoencephalocele.
Case reports: Cases 1 to 3 were born with a weight of between 2,300 to 3,202 g at gestation week 38 to 41. There was no prenatal diagnosis in any of the cases. All three cases were diagnosed with meningoencephalocele based on CT and MRI after they exhibited respiratory disorders. Cases 1 and 2 received tracheal intubation on days 15 and 7, respectively. Case 3 exhibited more severe airway obstruction because of tumor in the oral cavity; therefore, tracheal intubation was performed immediately after birth. A surgical repair was performed on day 25 to 34. All three patients were accompanied by hypertelorisms and optic nerve abnormalities. Additionally, Case 1 had cheilognathopalatoschisis, and Case 3 had cheilognathopalatoschisis and epignathus. For the assessment of occult postoperative cerebrospinal fluid leakage, nuclear count with 111In-cisternoscintigraphy was performed.
Conclusion: Meningoencephalocele increases the risk of respiratory obstruction and meningitis. Therefore, it is important to suspect its diagnosis based on respiratory disorder, oral mass, and midfacial abnormalities such as hypertelorism and cheilognathopalatoschisis. When the oral cavity or respiratory tract is severely occluded as seen in Case 3, tracheotomy can be an important option for safe performance of surgery in the oral cavity.
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Case Report
Title
The Use of Continuous Subcutaneous Insulin Infusion Therapy in a 1 Year-old Type 1 Diabetes Boy with Down Syndrome
Author
Aoi Kawakita Yukiyo Yamamoto Ryota Igarashi Mami Eguchi Motohide Goto Masahiro Ishii Takayuki Hoshina and Koichi Kusuhara
Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health
Abstract
Continuous subcutaneous insulin infusion (CSII) has been shown to be safe and effective for pediatric as well as adult patients with type 1 diabetes. Here, we report an infant case with Down syndrome treated with CSII and carbohydrate counting. A 1 year-old boy with Down syndrome was given a diagnosis of type 1 diabetes, and insulin replacement using multiple daily injections (MDI) was started. However, MDI therapy failed to reach adequate glycemic control despite frequent injections. This was most likely due to a limit in the fine-adjustment capability of small insulin doses. After one week, MDI therapy was replaced by CSII. Better glycemic control was achieved with reduced episodes of hypoglycemia and relief from the stress related to frequent insulin injection. Importantly, fine adjustment of small insulin doses with CSII, together with carbohydrate counting, allowed for fluctuations in the food and milk intake. We suggest that CSII is beneficial for patients with Down syndrome, especially infant cases.
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Case Report
Title
5, 10-methylenetetrahydrofolate Reductase Deficiency in an Infant with Rapidly Progressive Brain Atrophication
Author
Keita Otsuka1) Toshiya Nishikubo1) Hitoshi Tonegawa1) Eri Nishimoto1) Takashi Nakagawa1) Tomoyuki Kamamoto1) Yumiko Uchida1) Takafumi Sakakibara2) Osamu Sakamoto3) and Yukihiro Takahashi1)
1)Division of Neonatal Intensive Care, Center for Perinatal Medicine, Nara Medical University Hospital
2)Department of Pediatrics, Nara Medical University Hospital
3)Department of Pediatrics, Tohoku University School of Medicine
Abstract
5, 10-methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare congenital folate metabolism disorder. We present the case of an infant with MTHFR deficiency who exhibited rapidly progressive brain atrophication.
The patient was born to non-consanguineous parents after an uneventful pregnancy. He was complicated with feeding difficulties and lethargy, and was admitted to our hospital at 5 days after birth. Routine blood examinations and neonatal mass screening produced normal findings. However, he suffered rapid brain atrophication when he was one month old. Blood metabolic workups detected a high plasma total homocysteine level (221.8 nmol/mL) and a low plasma methionine level (4.3 nmol/mL). Molecular genetic analysis of the MTHFR gene identified compound heterozygosity for c.1122C>G and c.1539dupA.
The oral administration of betaine (100 mg/kg/day twice a day), folate (5 mg/day), vitamin B6 (50 mg/day), vitamin B2 (5 mg/day), and carnitine (200 mg/day) was commenced together with the intramuscular administration of hydroxocobalamin (1 mg/day). The administration frequency of betaine was subsequently increased to 4 times a day, which resulted in marked reductions in the patient's plasma homocysteine levels. Methionine (230 mg/day) supplementation (in addition to betaine therapy) was necessary to normalize the patient's plasma methionine levels.
In infants with unexplained feeding difficulties and lethargy, clinicians should pay attention to congenital folate metabolism disorders such as MTHFR deficiency. We consider that the detection of low methionine blood levels during neonatal mass screening should be treated as a warning sign of such conditions.
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Case Report
Title
Six Cases of Enterovirus D68 Infection Including Acute Flaccid Paralysis
Author
Satomi Mori Mitsuru Endo Yuri Uchida Eri Konishi and Hitoshi Sejima
Department of Pediatrics, Matsue Red Cross Hospital
Abstract
Enterovirus D68 (EV-D68) is known to cause respiratory tract infection. In 2014 a number of countries experienced outbreaks of EV-D68-that was associated with severe respiratory symptoms. EV-D68 was also identified in Japanese patients suffering from acute respiratory failure, bronchial asthma attack and acute flaccid paralysis in 2015. We report clinical manifestation of 6 children with EV-D68 infection.
Thirty five children with bronchial asthma attack were hospitalized from August to November 2015 in our hospital, Shimane, Japan. This number of patients was remarkably higher compared to the past three years. EV-D68 was detected from the nasopharyngeal aspirate specimens in 6 patients. It suggested that EV-D68 was related to the increase of hospitalization for bronchial asthma attack.
All six patients were more likely to present with wheeze and cough. Three patients required isoproterenol inhalation. Another girl who had severe respiratory failure required mechanical ventilation, followed by the sudden development of flaccid paralysis of lower and upper extremities. Her paralysis did not resolve, in spite of corticosteroid pulse therapy and intravenous immunoglobulin.
EV-D68 children tended to have severe respiratory symptom. Our cases suggest that EV-D68 contributed to the increase in number of patients with bronchial asthma attack and that development of acute flaccid paralysis. Monitoring and investigation of EV-D68 are necessary to predict severe respiratory disease and acute flaccid paralysis.
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Case Report
Title
A Case of SLE Associated Lupus Anticoagulant Hypoprothrombinemia Syndrome with Epistaxis as an Initial Symptom
Author
Sota Masuoka1) Shuji Kondo2)3) Takafumi Okada3) Akito Yokoyama3) Tsuyako Iwai3) Asayuki Iwai3) and Ichiro Yokota3)
1)Department of Education and Training, Shikoku Medical Center for Children and Adults
2)Department of Pediatric Nephrology, Shikoku Medical Center for Children and Adults
3)Department of Pediatrics, Shikoku Medical Center for Children and Adults
Abstract
Lupus anticoagulant (LA) is detected in patients with an autoimmune disease such as systemic lupus erythematosus (SLE) and some infectious diseases. It is strongly associated with anti-phospholipid antibody syndrome, which leads to a thrombotic condition. On the other hand, it may cause bleeding symptoms in lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) associated with LA-positive hypoprothrombinemia.
A 15-year-old girl frequently experienced nasal hemorrhage that had continued for more than an hour per episode. Extended PT and APTT were detected. Cross-mixing tests showed an inhibitor pattern, and LA was positive. Additional findings, including hypocomplementemia and elevated anti-ds-DNA antibody, resulted in diagnosis of SLE. Decreased activity of factor II (prothrombin) and the positive anti-prothrombin antibody indicated that abnormal bleeding was caused by LAHPS complicated by SLE. Although other anti-phospholipid antibodies, including LA, were positive, thrombotic complication was not recognized. After treatment for SLE, PT, APTT, and factor II activity improved, and no bleeding symptoms such as nasal hemorrhage were observed.
LAHPS associated with viral infection is transient, and cured without treatment. On the other hand, LAHPS associated with autoimmune disease shows persistent symptoms, and requires treatment. Deaths and recurrent cases have also been reported. Even if the bleeding symptoms of a patient do not seem life-threatening, LAHPS should be considered in cases that are LA-positive with extended PT and APTT.
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