Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.
Anastasios SerbisDimitrios RallisVasileios GiaprosAssimina Galli-TsinopoulouEkaterini SiomouPublished in: International journal of molecular sciences (2023)
Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease caused by mutations in WFS1 and WFS2 genes that produce wolframin, a protein involved in endoplasmic reticulum calcium homeostasis and cellular apoptosis. Its main clinical features are diabetes insipidus (DI), early-onset non-autoimmune insulin-dependent diabetes mellitus (DM), gradual loss of vision due to optic atrophy (OA) and deafness (D), hence the acronym DIDMOAD. Several other features from different systems have been reported such as urinary tract, neurological, and psychiatric abnormalities. In addition, endocrine disorders that can appear during childhood and adolescence include primary gonadal atrophy and hypergonadotropic hypogonadism in males and menstrual cycle abnormalities in females. Further, anterior pituitary dysfunction with deficient GH and/or ACTH production have been described. Despite the lack of specific treatment for the disease and its poor life expectancy, early diagnosis and supportive care is important for timely identifying and adequately managing its progressive symptoms. The current narrative review focuses on the pathophysiology and the clinical features of the disease, with a special emphasis on its endocrine abnormalities that appear during childhood and adolescence. Further, therapeutic interventions that have been proven to be effective in the management of WS1 endocrine complications are discussed.
Keyphrases
- early onset
- type diabetes
- glycemic control
- endoplasmic reticulum
- oxidative stress
- multiple sclerosis
- depressive symptoms
- urinary tract
- late onset
- healthcare
- cardiovascular disease
- mental health
- palliative care
- endoplasmic reticulum stress
- childhood cancer
- case report
- risk factors
- physical activity
- quality improvement
- replacement therapy
- optical coherence tomography
- dna methylation
- early life
- knee osteoarthritis
- pseudomonas aeruginosa
- insulin resistance
- skeletal muscle
- staphylococcus aureus
- transcription factor
- duchenne muscular dystrophy
- binding protein
- blood brain barrier
- young adults
- weight loss
- cerebral ischemia
- smoking cessation