Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency.

Nicotinamide nucleotide transhydrogenase (NNT) deficiency causes primary adrenal insufficiency (PAI) and possibly some extra-adrenal manifestations. A limited number of these patients were previously described. We present the clinical and genetic characteristics of three family members with a biallelic novel pathogenic variant in the NNT gene. The patients were followed until the ages of 21.6, 20.2, and 4.2 years. PAI was diagnosed in the eldest two brothers after an Addisonian crisis and the third was diagnosed at the age of 4.5 months in the asymptomatic stage due to the genetic screening of family members. Whole exome sequencing with a targeted interpretation of variants in genes related to PAI was performed in all the patients. The urinary steroid metabolome was determined by gas chromatography-mass spectrometry in the asymptomatic patient. The three patients, who were homozygous for c.1575dup in the NNT gene, developed isolated glucocorticoid deficiency. The urinary steroid metabolome showed normal excretion of cortisol metabolites. The adolescent patients had slow pubertal progression with low-normal testicular volume, while testicular endocrine function was normal. Bone mineral density was in the range for osteopenia in both grown-up siblings. Echocardiography revealed no structural or functional heart abnormalities. This article is among the first with a comprehensive and chronologically-detailed description of patients with NNT deficiency.

Brain Aneurysms in the Pediatric Population of Slovenia: A Case Series.

BACKGROUND: Brain aneurysms are rare in the pediatric population. The diagnosis of a brain aneurysm in a child may be difficult because of its infrequency and often subtle or nonspecific clinical presentation. Endovascular therapy and microsurgical treatment are increasingly used approaches in treating children, possibly contributing to favorable outcomes if patients are treated in a timely manner. OBJECTIVE: We were interested in the clinical presentation, symptoms, diagnostics, treatment, and follow-up of pediatric patients with brain aneurysms in Slovenia. METHODS: This was a retrospective review of medical documentation of children with intracranial aneurysms treated at the University Children's Hospital in Ljubljana, Slovenia, from January 1998 to December 2017. RESULTS: We identified a cohort of eight children (median age: 14.9 years; range: 2.8-17.7). The estimated incidence of pediatric brain aneurysms in Slovenia is 0.12/100,000 children per year. We observed a male predominance (1.7:1). Half of the patients presented with acute onset of neurologic symptoms and three with subarachnoid hemorrhage. One of the patients had a related stroke. The presenting symptoms were tonic-clonic seizures, hemiparesis, paresthesias, speech disturbance, and cranial nerve palsy. The other half of aneurysms were identified incidentally. Five patients had anterior circulation aneurysms; the most prevalent location was the internal carotid artery. One patient was treated with surgical procedures, four patients were treated with endovascular procedures, and three patients were treated conservatively. Outcome was excellent in all patients. CONCLUSION: Endovascular interventions and microsurgical procedures appear to be safe and effective in the treatment of brain aneurysms in the pediatric population. Asymptomatic patients with brain aneurysms need close follow-up.

Biofeedback for treatment of awake and sleep bruxism in adults: systematic review protocol.

BACKGROUND: Bruxism is a disorder of jaw-muscle activity characterised by repetitive clenching or grinding of the teeth which results in discomfort and damage to dentition. The two clinical manifestations of the condition (sleep and awake bruxism) are thought to have unrelated aetiologies but are palliated using similar techniques. The lack of a definitive treatment has prompted renewed interest in biofeedback, a behaviour change method that uses electronic detection to provide a stimulus whenever bruxism occurs. This systematic review aims to provide a comprehensive overview of the state of research into biofeedback for bruxism; to assess the efficacy and acceptability of biofeedback therapy in management of awake bruxism and, separately, sleep bruxism in adults; and to compare findings between the two variants. METHODS: A systematic review of published literature examining biofeedback as an intervention directed at controlling primary bruxism in adults. We will search electronic databases and the grey literature using a predefined search strategy to identify randomised and non-randomised studies, technical reports and patents. Searches will not be restricted by language or date and will be expanded through contact with authors and experts, and by following up reference lists and citations. Two authors, working independently, will conduct screening of search results, study selection, data extraction and quality assessment and a third will resolve any disagreements. The primary outcomes of acceptability and effectiveness will be assessed using only randomised studies, segregated by bruxism subtype. A meta-analysis of these data will be conducted only if pre-defined conditions for quality and heterogeneity are met, otherwise the data will be summarized in narrative form. Data from non-randomised studies will be used to augment a narrative synthesis of the state of technical developments and any safety-related issues. PROSPERO registration number: CRD42013006880. DISCUSSION: Biofeedback is not new, but its place in the clinical management of bruxism remains unclear. New research, and the availability of miniaturized consumer-grade devices, makes a systematic review timely to guide treatment decisions and inform future research.