Carney Complex Complicated with Primary Pigmented Nodular Adrenocortical Disease without Cushing's Syndrome Recurrence for Five Years after Unilateral Adrenalectomy.

We herein report a case of Carney complex (CNC) complicated with primary pigmented nodular adrenocortical disease (PPNAD) after unilateral adrenalectomy. A 44-year-old woman was admitted to our hospital for PPNAD surgery. She had previously undergone surgery for cardiac myxoma and had a PRKAR1A mutation with no family history of CNC. She had Cushing's signs, but her metabolic abnormalities were mild. Adrenal insufficiency due to poor medication adherence was a concern, so she underwent unilateral adrenalectomy. Cushing's signs improved postoperatively and without recurrence for five years. Treatment plans for PPNAD should be determined based on the patient's condition, medication adherence, and wishes.

Temporal requirement of dystroglycan glycosylation during brain development and rescue of severe cortical dysplasia via gene delivery in the fetal stage.

Congenital muscular dystrophies (CMDs) are characterized by progressive weakness and degeneration of skeletal muscle. In several forms of CMD, abnormal glycosylation of α-dystroglycan (α-DG) results in conditions collectively known as dystroglycanopathies, which are associated with central nervous system involvement. We recently demonstrated that fukutin, the gene responsible for Fukuyama congenital muscular dystrophy, encodes the ribitol-phosphate transferase essential for dystroglycan function. Brain pathology in patients with dystroglycanopathy typically includes cobblestone lissencephaly, mental retardation, and refractory epilepsy; however, some patients exhibit average intelligence, with few or almost no structural defects. Currently, there is no effective treatment for dystroglycanopathy, and the mechanisms underlying the generation of this broad clinical spectrum remain unknown. Here, we analysed four distinct mouse models of dystroglycanopathy: two brain-selective fukutin conditional knockout strains (neuronal stem cell-selective Nestin-fukutin-cKO and forebrain-selective Emx1-fukutin-cKO), a FukutinHp strain with the founder retrotransposal insertion in the fukutin gene, and a spontaneous Large-mutant Largemyd strain. These models exhibit variations in the severity of brain pathology, replicating the clinical heterogeneity of dystroglycanopathy. Immunofluorescence analysis of the developing cortex suggested that residual glycosylation of α-DG at embryonic day 13.5 (E13.5), when cortical dysplasia is not yet apparent, may contribute to subsequent phenotypic heterogeneity. Surprisingly, delivery of fukutin or Large into the brains of mice at E12.5 prevented severe brain malformation in Emx1-fukutin-cKO and Largemyd/myd mice, respectively. These findings indicate that spatiotemporal persistence of functionally glycosylated α-DG may be crucial for brain development and modulation of glycosylation during the fetal stage could be a potential therapeutic strategy for dystroglycanopathy.

Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate-ectodermal dysplasia syndrome in an Asian patient.

Cleft lip/palate-ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss-of-function mutations of the poliovirus receptor-like 1 (PVRL1) gene encoding nectin-1. Nectin-1 is a cell-cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate-ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7-year-old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate-ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin-1, which is necessary to initiate the cell-cell adhesion process.

[A case of an elderly diabetic patient with dementia effectively treated with weekly exenatide].

A 74-year-old man with diabetes mellitus since 64 years of age had been treated with glimepiride, metformin and alogliptin; however, his glycemic control remained poor, i.e., a casual blood glucose level of 318 mg/dl, HbA1c level of 10.6% and glycated albumin level of 24.9%. Although his blood glucose level improved with intensive insulin therapy, he exhibited dementia with an MMSE score of 9/30 and was unable to continue insulin injections by himself, thus rejecting his family's help. The extended-release form of the GLP-1 agonist exenatide (Bydureon(®)) was recently introduced in Japan. This new anti-diabetic agent enables the administration of once-weekly type 2 diabetes treatment that delivers a continuous dose of exenatide in a single weekly injection. We employed weekly exenatide therapy in combination with oral hypoglycemic agents in this case. The patient visited our outpatient clinic for injections every week, showing a remarkable improvement in his HbA1c level, from 10.7% to 7.1% in five months. Subcutaneous induration was the only side effect of weekly exenatide injection. Weekly exenatide therapy can be easily managed by other caregivers and is expected to be a useful treatment approach in elderly diabetic patients with dementia.

[Bone metabolism and cardiovascular function update. Effects of antiosteoporotic agents on glucose and lipid metabolism].

At present, antiosteoporotic agents that might affect glucose and/or lipid metabolism include bisphosphonates, Selective Estrogen Receptor Modulators ; SERMs and activated vitamin D. Bisphosphonates have little, if any, effect on lipid metabolism, while they are suggested to improve glucose metabolism, via osteocalcin or adiponectin. SERMs are shown to decrease serum triglycerides and LDL cholesterol levels, and increase HDL cholesterol level. To date, SERMs are not proven to reduce the risk of coronary events. From nutritional point of view, studies suggest that vitamin D may improve lipid and glucose metabolism, whereas its therapeutic effect on lifestyle related diseases is unknown.