Ishii T.,Keio University |
Anzo M.,Kawasaki City Hospital |
Adachi M.,Kanagawa Childrens Medical Center |
Onigata K.,The University of Shimane |
And 10 more authors.
Clinical Pediatric Endocrinology | Year: 2015
Purpose of developing the guidelines: The first guidelines for diagnosis and treatment of 21-hydroxylase deficiency (21-OHD) were published as a diagnostic handbook in Japan in 1989, with a focus on patients with severe disease. The “Guidelines for Treatment of Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) Found in Neonatal Mass Screening (1999 revision)” published in 1999 were revised to include 21-OHD patients with very mild or no clinical symptoms. Accumulation of cases and experience has subsequently improved diagnosis and treatment of the disease. Based on these findings, the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology further revised the guidelines for diagnosis and treatment. Target disease/conditions: 21-hydroxylase deficiency. Users of the guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, referring pediatric practitioners, general physicians; and patients. © 2015, by The Japanese Society for Pediatric Endocrinology.
Hintze J.P.,Saint Louis University |
Tomatsu S.,Saint Louis University |
Fujii T.,Sapporo IDL |
Montano A.M.,Saint Louis University |
And 5 more authors.
Biomarker Insights | Year: 2011
Background and aim: Mucopolysaccharidosis IVA (MPS IVA) leads to skeletal dysplasia through excessive storage of chondroitin-6-sulfate and keratan sulfate (KS). KS is synthesized mainly in cartilage and released into circulation, making it a critical biomarker for MPS IVA to evaluate clinical course and effectiveness of therapies. Therefore, an accurate and sensitive method is required to measure KS levels. Material and methods: Using sandwich ELISA and liquid chromatography tandem mass spectrometry (LC/MS/MS) assays, we measured KS levels in blood and urine from MPS IVA patients and healthy controls to evaluate comparability of results. Blood (patients, n = 110; controls, n = 364) and urine (patients, n = 103; controls, n = 326) specimens were obtained. Results: Plasma and urine KS measurements in patients were age-dependent and higher than age-matched controls. We observed a moderate correlation (r = 0.666; P, 0.001) between urine KS measurements and a weak correlation (r = 0.333; P = 0.002) between plasma KS measurements by ELISA and LC/MS/MS methods in patients. No correlation was found between plasma KS measurements in controls. The difference between KS measurements assayed by LC/MS/MS and ELISA was greater in controls than in patients. A moderate correlation between blood and urine KS measurements in the same individual was observed. Conclusion: These findings indicate that both methods to measure blood and urine KS are suitable for diagnosis, monitoring therapies, and longitudinal assessment of the disease course in MPS IVA, but the LC/MS/MS method measures over 10 times more KS present in body fluids. © the author(s), publisher and licensee Libertas Academica Ltd.
Tajima T.,Hokkaido University |
Tajima T.,Jichi Childrens Medical Center Tochigi |
Fukushi M.,Sapporo IDL
Clinical Pediatric Endocrinology | Year: 2016
Congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency (21-OHD) is an inherited autosomal recessive disorder. Its incidence is 1 in 10,000 to 20,000 worldwide. This disease shows phenotypic differences, and it is divided into three forms i.e., the salt wasting (SW), simple virilizing (SV), and nonclassic (NC) forms. The most severe form of SW manifests in the first months of life with life-threatening adrenal insufficiency, leading to death. To prevent death by adrenal insufficiency in neonates with the SW form and wrong gender assignment of 46,XX female patients with SW and SV, neonatal mass screening of 21-OHD is performed in several countries including Japan. However, the positive predictive value (PPV) remains low, especially in preterm infants. To reduce the false positive rate and increase the PPV, liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) as a second-tier test may be useful. In this review, the current knowledge on neonatal mass screening of 21-OHD is summarized. © 2016 by The Japanese Society for Pediatric Endocrinology.
Tomatsu S.,DuPont Company |
Fujii T.,Sapporo IDL |
Fukushi M.,Sapporo IDL |
Oguma T.,Daiichi Sankyo |
And 10 more authors.
Molecular Genetics and Metabolism | Year: 2013
Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence of higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death. MPS disorders are potentially treatable with enzyme replacement therapy or hematopoietic stem cell transplantation. For maximum benefit of available therapies, early detection and intervention are critical.We recently developed a novel high-throughput multiplex method to assay DS, HS, and KS simultaneously in blood samples by using high performance liquid chromatography/tandem mass spectrometry for MPS. The overall performance metrics of HS and DS values on MPS I, II, and VII patients vs. healthy controls at newborns were as follows using a given set of cut-off values: sensitivity, 100%; specificity, 98.5-99.4%; positive predictive value, 54.5-75%; false positive rate, 0.62-1.54%; and false negative rate, 0%. These findings show that the combined measurements of these three GAGs are sensitive and specific for detecting all types of MPS with acceptable false negative/positive rates. In addition, this method will also be used for monitoring therapeutic efficacy. We review the history of GAG assay and application to diagnosis for MPS. © 2013 Elsevier Inc.