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
- multiple sclerosis
- oxidative stress
- depressive symptoms
- healthcare
- late onset
- urinary tract
- case report
- cardiovascular disease
- physical activity
- palliative care
- mental health
- autism spectrum disorder
- risk factors
- endoplasmic reticulum stress
- cell death
- gene expression
- staphylococcus aureus
- optical coherence tomography
- chronic pain
- knee osteoarthritis
- combination therapy
- muscular dystrophy
- binding protein
- signaling pathway