Recent trend toward decrease in the incidence of childhood type 2 diabetes in Tokyo.
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Adolescent↗
Biomedical subjects
Teruo Kitagawa
Publications and source records attributed to Teruo Kitagawa.
Non-invasive screening method for Fabry disease by measuring globotriaosylceramide in whole urine samples using tandem mass spectrometry.
Fabry disease is an X-linked sphingolipidosis due to a deficiency of alpha-galactosidase A, which leads to the accumulation of globotriaosylceramide (GL-3) in several organs. When recombinant human alpha-galactosidase A is intravenously administered repeatedly before the patient develops permanent tissue damage, there is evidence that the accumulation of GL-3 is decreased in some organs and that the clinical symptoms are alleviated in some patients. However, Fabry disease is rare and many patients are not diagnosed until adulthood after irreversible tissue damage has occurred. Our group has developed a simple and non-invasive screening method for Fabry disease that measures total GL-3 in whole urine samples by tandem mass spectrometry. Using this method, we found that the concentration of GL-3 in whole urine sample from hemizygous patients, including pre-symptomatic young children with classic type Fabry disease, was significantly higher than that in controls. The mean concentration of GL-3 in urine from heterozygotes with symptoms was significantly higher than control concentrations, but GL-3 levels in the urine from 2 out of 8 heterozygotes of classic type Fabry disease were within control levels. An asymptomatic 14-year old hemizygote in the family of a cardiac variant did not have elevated urinary GL-3. Therefore, screening for the classic type and probably renal variant of Fabry disease is possible by measuring urinary GL-3, using our method. The early diagnosis of cardiac variant hemizygotes and some heterozygotes with all types of Fabry disease will not be possible using our method. We propose that this procedure can be used as a reliable, non-invasive, simple method for general and high-risk population screening for hemizygotic patients with the classic type and probably renal variant of Fabry disease.
Adolescent↗
Annual incidence and clinical characteristics of type 2 diabetes in children as detected by urine glucose screening in the Tokyo metropolitan area.
OBJECTIVE: This study investigates the annual incidence and clinical characteristics of type 2 diabetes among school-aged children as detected by urine glucose screening from 1974 to 2002 in the Tokyo metropolitan area. RESEARCH DESIGN AND METHODS: In total, 8,812,356 school children were examined for glucosuria. Morning urine was used for the analysis. When the urine was positive for glucose, an oral glucose tolerance test was carried out to confirm diabetes. RESULTS: In all, 232 students were identified to have type 2 diabetes. The overall annual incidence of type 2 diabetes was 2.63/100,000. The annual incidence after 1981 was significantly higher than that before 1980 (1.73 vs. 2.76/100,000, P < 0.0001). The annual incidence was significantly higher for junior high school students compared with primary school students (0.78 vs. 6.43/100,000, P < 0.0001). The overall male-to-female ratio of students with type 2 diabetes was 1.0:1.19 (P = 0.296), but it was 1.0:1.56 (P = 0.278) for primary school students. Overall, 83.4% of children with diabetes were obese (> or = 20% overweight). However, nonobese girls (<20% overweight) with diabetes accounted for 23.0% of the patients, whereas markedly obese boys (> or = 40% overweight) accounted for 61.5% of the patients. The frequency of a family history of type 2 diabetes in second- and first-degree relatives was 56.5%. CONCLUSIONS: We confirmed that the incidence of young people with type 2 diabetes increased after 1981 in the Tokyo metropolitan area. The increase in the frequency of this disorder seemed to be strongly related to an increasing prevalence of obesity. Age and genetic susceptibility may be associated with the occurrence of type 2 diabetes.
Adolescent↗
Usefulness of an automated urinary flow cytometer in mass screening for nephritis.
We aimed to assess the utility of a newly developed automated urinary flow cytometer (UFCM) in differentiating the origin of hematuria in the mass screening system for renal diseases in school children. In total, 4,620 children aged 6-14 years with abnormal urinary findings by the screening program in Tokyo were enrolled. Tentative diagnoses were made based on the criteria for this screening program: nephritis in 11, suspected nephritis in 104, hematuria in 771, minimal hematuria in 1,506, proteinuria in 477, urinary tract infection in 83, and healthy in 1,668. Glomerular hematuria, assessed by UFCM, was found in 81.8% of nephritis, 58.7% of suspected nephritis, 59.7% of hematuria, 57.4% of minimal hematuria, 13.4% of proteinuria, and 21.5% of the healthy group. The presence of glomerular hematuria assessed by UFCM had a sensitivity of 61.0%, specificity of 78.5%, positive predictive value of 16.3%, and negative predictive value of 96.7% for the diagnosis of nephritis and suspected nephritis. Thus, our results imply that the absence of glomerular hematuria as assessed by UFCM is highly predictive of the absence of nephritis. If "healthy" children with non-glomerular hematuria by UFCM could be excluded, the total annual cost saving would be approximately 147.4 million JPY, which is equivalent to 5.2% of the current system. In conclusion, a simple, automated and rapid test for glomerular hematuria using UFCM is useful for mass screening. It can precisely predict children with only transient hematuria who do not have any serious illness, and therefore can exclude further unnecessary examinations, resulting in the improvement of cost-effectiveness of the current program.
Adolescent↗
Long-term treatment and diagnosis of tetrahydrobiopterin-responsive hyperphenylalaninemia with a mutant phenylalanine hydroxylase gene.
A novel therapeutic strategy for phenylketonuria (PKU) has been initiated in Japan. A total of 12 patients who met the criteria for tetrahydrobiopterin (BH(4))-responsive hyperphenylalaninemia (HPA) with a mutant phenylalanine hydroxylase (PAH) (EC 1.14.16.1) gene were recruited at 12 medical centers in Japan between June 1995 and July 2001. Therapeutic efficacy of BH(4) was evaluated in single-dose, four-dose, and 1-wk BH(4) loading tests followed by long-term BH(4) treatment, and also examined in relation to the PAH gene mutations. The endpoints were determined as the percentage decline in serum phenylalanine from initial values after single-dose (>20%), four-dose (>30%), and 1-wk BH(4) (>50%) loading tests. Patients with mild PKU exhibiting decreases in blood phenylalanine concentrations of >20% in the single-dose test also demonstrated decreases of >30% in the four-dose test. The 1-wk test elicited BH(4) responsiveness even in patients with poor responses in the shorter tests. Patients with mild HPA, many of whom carry the R241C allele, responded to BH(4) administration. No clear correlation was noted between the degree of decrease in serum phenylalanine concentrations in the single- or four-dose tests and specific PAH mutations. The 1-wk test (20 mg/kg of BH(4) per day) is the most sensitive test for the diagnosis of BH(4)-responsive PAH deficiency. Responsiveness apparently depends on mutations in the PAH gene causing mild PKU, such as R241C. BH(4) proved to be an effective therapy that may be able to replace or liberalize the phenylalanine-restricted diets for a considerable number of patients with mild PKU.
Biopterins↗
Mass screening for Wilson's disease by measuring urinary holoceruloplasmin.
We conducted a mass-screening method to detect presymptomatic Wilson's disease in children by measuring urinary holoceruloplasmin. Two cases of Wilson's disease were found by testing urine samples from 48,819 children. The diagnosis was confirmed by clinical laboratory tests and the detection of a mutated ATP 7B gene.
Adolescent↗
Low prevalence of hypercalciuria in Japanese children.
BACKGROUND/AIM: There are several factors, such as race, age, sex, and geographical variations, associated with renal stone formation. Although it is known that the prevalence of urolithiasis in Japanese children is low, the reason remains obscure. We hypothesize that the low prevalence of urolithiasis is associated with the urinary calcium excretion. The aim of our study was to investigate the prevalence of hypercalciuria in Japanese children. METHODS: This investigation is a population-based school survey. A group of 529 healthy Japanese children was screened for hypercalciuria by measurement of the urinary Ca/Cr ratio using the morning fasting urine. In addition, the urinary Na/Cr ratio was also calculated for each subject. RESULTS: Hypercalciuria regarded as an urinary Ca/Cr value of more than 0.17 was noted only in 3 out of 529 children (0.6 %), while most cases (494/529, 93.4%) demonstrated hypocalciuria (urinary Ca/Cr <0.05). The mean urinary Ca/Cr value was 0.024 in all subjects combined. Linear regression analysis revealed a positive direct correlation between urinary Ca/Cr and Na/Cr values (rs = 0.14, p < 0.01). The urinary Ca/Cr ratio was not related to age in either sex. CONCLUSIONS: The present study demonstrates that the prevalence of hypercalciuria in Japanese children is low as compared with other countries, even though absorptive hypercalciuria and dietary hypercalciuria might be missed in this setting. This low prevalence of hypercalciuria may be associated with the lower prevalence of urolithiasis in Japanese children. As it is suggested that a low dietary intake of calcium and sodium may play some role in the low urinary calcium excretion, a randomized, controlled study comparing the efficacy of different modes of therapy, such as a low-calcium diet and/or a low-salt diet, might provide valuable information for the prevention of urolithiasis.
Calcium↗