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A Japanese woman aged in her late 30s with severe insulin resistance and bodily features including a triangular face, prominent forehead, small chin, large and low‐set ears, and ocular depression was investigated. A similar phenotype was not observed in other family members with the exception of her son, suggesting that the condition was caused by a de novo mutation that was transmitted from mother to son. Exome analysis showed the presence in the proband and her son of a c.1945C>T mutation in PIK3R1, a common mutation associated with SHORT (short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay) syndrome. Administration of a sodium–glucose cotransporter 2 inhibitor lowered the proband's hemoglobin A1c level and allowed a reduction in her insulin dose without treatment‐related adverse events including ketoacidosis, exaggerated loss of body mass or hypoglycemia. Sodium–glucose cotransporter 2 inhibitors might thus offer an additional option for the treatment of genetic syndromes of severe insulin resistance.

Background Glutaryl carnitine (C5DC) in dried blood spots is used as a biomarker for glutaric aciduria type 1 (GA-1) screening. C5DC, however, is the only screening marker for this condition, and various pathological conditions may interfere with C5DC metabolism. Recently, C5DC elevation has been reported in cases of renal insufficiency. Method Five patients who were positive for GA-1 on newborn screening with tandem mass spectrometry between September 2012 and March 2015 at Kobe University Hospital were enrolled in this study. Results GA-1 was not confirmed on urinary organic acids analysis in any of the patients. C5DC decreased immediately in four patients, but one patient, who had high C5DC for at least 4 months, was diagnosed with bilateral renal hypoplasia. Conclusion In the case of persistently elevated C5DC, renal insufficiency should be considered as a differential diagnosis.

Background: The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen’s original article was published in 1912. Methods: We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease. Results: Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35βH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas. Conclusions: Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis.

Oxidized LDL has been obtained by incubation with copper ions (Cu-LDL) or various kinds of cells. LDL incubated with xanthoma tissues (x-LDL) is considered a model of in vivo oxidized LDL that has extravasated into xanthoma lesions. To investigate the mechanism of x-LDL formation, we studied the effects of various enzyme inhibitors or antioxidants on the oxidation process of LDL. Thiobarbituric acid-reactive substance (TBARS) levels, electrophoretic mobility and spectrophotometric pattern of the oxidized LDL were examined. Antioxidants suppressed TBARS formation in both x-LDL and Cu-LDL. Enzyme inhibitors inhibited TBARS levels in x-LDL, but not in Cu-LDL. All the enzyme inhibitors and antioxidants, except for the cyclooxygenase inhibitor, inhibited the anodic electrophoretic mobility of x-LDL. The anodic electrophoretic mobility of Cu-LDL was suppressed only with antioxidants. Spectrophotometry indicated that an increase in the absorbance at 240 nm was observed in Cu-LDL, but not in x-LDL. x-LDL oxidation is primarily catalyzed by phospholipase A 2 , and subsequently generated polyunsaturated free fatty acids propagate the peroxidation. Fatty acid hydroperoxides conjugated with dienes are not synthesized in x-LDL. On the other hand, non-enzymatic oxidants, such as superoxide anion and hydroxyl radicals generate Cu-LDL with diene-conjugated fatty acid hydroperoxides.