Outcomes of pediatric obesity-related lifestyle disease screenings in Kumamoto.

BACKGROUND: Obesity is an important issue causing both health hazards and socioeconomic loss to those affected. Kumamoto City regularly performs obesity-related lifestyle disease screenings for fourth grade children with obesity, including physical examinations, blood tests, and special examination referrals. We retrospectively analyzed the outcomes of the screenings conducted from 2011 to 2020. METHODS: The percentage of overweight was calculated using data from the Lifestyle Disease Screening Board of Kumamoto City from 2011 to 2020. The percentage of overweight, abdominal circumference, blood pressure, and laboratory test outcomes of the Secondary Lifestyle Disease Test were evaluated. RESULTS: The proportion of children with obesity in grades 1-4 in Kumamoto was higher than the national average, while that in grades 5-6 was lower than the national average. Among the fourth graders screened, 6521 were eligible for the Secondary Lifestyle Disease Tests, of which 3291 children underwent the test. In the testing, 22.3% of the boys and 29.1% of the girls were nonobese. Moreover, 25.9% of the boys and 19.2% of the girls, including nonobese children, required further examination and intervention. Notably, 62.1% of the boys and 46.2% of the girls who were nonobese and required special examination had a waist circumference of ≥75 cm or waist-to-height ratios of ≥0.5. CONCLUSIONS: Obesity-related lifestyle disease screenings contributed to preventing obesity progression. Abdominal circumference measurements may be useful in determining nonobese children at a risk of lifestyle diseases.

Hyperprolinemia type I caused by homozygous p.T466M mutation in PRODH.

Hyperprolinemia type I (HPI) is an autosomal recessive metabolic disorder caused by defects in proline oxidase. We herein describe a case of a patient with HPI and harboring the NM_016335.4 (PRODH_v001):c.1397 C > T (p.T466M) mutation and polymorphisms in the PRODH gene, as detected by plasma amino acid analysis and Sanger sequencing. The patient presented with short stature, carbohydrate-rich dietary preferences, and mild intellectual disability that was suggestive of a neurodevelopmental or learning disorder.

Phenotypes of a family with XLH with a novel PHEX mutation.

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. We encountered a 4-year-old boy with a novel variant in the phosphate-regulating neutral endopeptidase homolog X-linked (PHEX) gene who presented with a short stature, genu valgum, and scaphocephaly. The same mutation was identified in his mother and sister; however, the patient presented with a more severe case.

Genetic defects in pediatric-onset adrenal insufficiency in Japan.

CONTEXT: Most patients with pediatric-onset primary adrenal insufficiency (PAI), such as 21-hydroxylase deficiency, can be diagnosed by measuring the urine or serum levels of steroid metabolites. However, the etiology is often difficult to determine in a subset of patients lacking characteristic biochemical findings. OBJECTIVE: To assess the frequency of genetic defects in Japanese children with biochemically uncharacterized PAI and characterize the phenotypes of mutation-carrying patients. METHODS: We enrolled 63 Japanese children (59 families) with biochemically uncharacterized PAI, and sequenced 12 PAI-associated genes. The pathogenicities of rare variants were assessed based on in silico analyses and structural modeling. We calculated the proportion of mutation-carrying patients according to demographic characteristics. RESULTS: We identified genetic defects in 50 (85%) families: STAR in 19, NR0B1 in 18, SAMD9 in seven, AAAS in two, NNT in two, MC2R in one and CDKN1C in one. NR0B1 defects were identified in 78% of the male patients that received both glucocorticoid and mineralocorticoid replacement therapy and had normal male external genitalia. STAR defects were identified in 67% of female and 9% of male patients. Seven of the 19 patients with STAR defects developed PAI at age two or older, out of whom, five did not have mineralocorticoid deficiency. CONCLUSIONS: Molecular testing elucidated the etiologies of most biochemically uncharacterized PAI patients. Genetic defects such as NR0B1 defects are presumed based on phenotypes, while others with broad phenotypic variability, such as STAR defects, are difficult to diagnose. Molecular testing is a rational approach to diagnosis in biochemically uncharacterized PAI patients.

A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.

OBJECTIVES: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated. METHODS: We analyzed the patients' genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed. RESULTS: The analysis showed that the patients homozygously retained a missense mutation, Gumacr;GC[435Gly]-->Aumacr;GC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced. CONCLUSION: These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450(C18) activities causes CMO II deficiency.