RESUMEN
BACKGROUND: Fabry disease (FD) is a lysosomal storage disease caused by a deficit of α-galactosidase A (GAL). Recently, plasma globotriaosylsphingosine (lyso-Gb3), a pathogenic analog of a substrate of GAL, has been suggested as a potential biomarker for FD, and disease severity scores, such as the Mainz Severity Score Index (MSSI), the Disease Severity Scoring System (DS3), and FASTEX (FAbry STabilization indEX), are useful tools for evaluating the severity of signs and symptoms in symptomatic FD patients. However, a more useful method of evaluating disease severity in early-diagnosed FD patients such as children, adult females, and asymptomatic patients is needed. Here, we proposed modified MSSI and DS3 scores to which we added phenotype, urinary mulberry bodies, and history of past pain attacks and examined the clinical usefulness of lyso-Gb3 and modified scores for early-diagnosed FD patients. RESULT: In 13 early-diagnosed FD patients, we developed modified MSSI and DS3 scores and examined the correlation of lifetime lyso-Gb3 exposure at diagnosis with the conventional or modified scores. Lifetime lyso-Gb3 exposure was positively correlated only with the modified DS3 score. Additionally, we examined the long-term changes in plasma lyso-Gb3 concentration and in conventional MSSI, DS3, and FASTEX. In males, plasma lyso-Gb3 concentration decreased more rapidly than in females. In all patients, the severity scores were mild and remained nearly stable throughout the follow-up period. CONCLUSION: Our data suggest that lifetime lyso-Gb3 exposure and the modified DS3 score are useful in early-diagnosed patients.
RESUMEN
Background: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), a hereditary gastric polyposis syndrome that presents with fundic gastric polyposis, is associated with an increased risk of gastric adenocarcinoma. The four patterns of point mutation in the adenomatous polyposis coli (APC) promoter 1B region have been identified as the cause of GAPPS. GAPPS was first reported in 2012, and only 33 families with GAPPS have been reported worldwide to date. Therefore, the clinical management for GAPPS are still controversial. We herein report two unrelated GAPPS families with the same point mutation site. Case Description: Total seven patients of two families had >100 carpeting polyps in the gastric body and fundus, and one of them (69-year-old female) had gastric adenocarcinoma. As a result of germline analysis, both families harbored a point mutation (c.-192A>G) in APC promoter 1B region, previously reported in only one family. Three of seven patients underwent total gastrectomy, and others were followed-up with regular esophagogastroduodenoscopy (EGD) and biopsy every 6 months. To summarize the reported cases, total 42 patients of 35 families have developed gastric adenocarcinoma. Conclusions: This report may contribute to determining the appropriate guidelines for the clinical practice of GAPPS. When EGD reveals gastric polyposis localized to the gastric body and fundus, it is important to obtain a detailed family history and perform germline mutational analysis. And more, point mutation type of our family cases was a rare pattern, suggested that c.-192A>G pattern might be a pathogenic variant.
RESUMEN
Oculofaciocardiodental syndrome is caused by variants in the BCL6 corepressor (BCOR) gene. We identified a novel heterozygous frameshift variant, NM_001123385.2(BCOR):c.2326del, that arose de novo in a Japanese girl with characteristic facial features, congenital heart disease, bilateral syndactyly of toes 2 and 3, congenital cataracts, dental abnormalities, and mild intellectual disability. Reports of BCOR variants are rare, and further case accumulation is warranted.