Metabolic Treatment of Wolfram Syndrome

Abstract

Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is non-autoimmune diabetes even if other clinical features (optic subatrophy, neurosensorial deafness, diabetes insipidus) may be present in an early state and may be diagnosed after diabetes’ onset. Prognosis is poor, and the death occurs at the median age of 39 years as a consequence of progressive respiratory impairment, secondary to brain atrophy and neurological failure. The aim of this paper is the description of the metabolic treatment of the WS. We reported the experience of long treatment in patients with this syndrome diagnosed in pediatric age and followed also in adult age. It is known that there is a correlation between metabolic control of diabetes, the onset of other associated symptoms, and the progression of the neurodegenerative alterations. Therefore, a multidisciplinary approach is necessary in order to prevent, treat and carefully monitor all the comorbidities that may occur. An extensive understanding of WS from pathophysiology to novel possible therapy is fundamental and further studies are needed to better manage this devastating disease and to guarantee to patients a better quality of life and a longer life expectancy.

Wolfram Syndrome: A Curious Case of Repetitive Loss of Consciousness

“…Most patients die prematurely, with the median age of death being 30 years [ 1 , 2 ]. This can be explained by the rapidly progressive clinical course of this disease, with brain stem atrophy and bulbar dysfunction appearing early in life [ 1 - 3 , 5 , 14 ]. This leads to respiratory failure and dysphagia, which can cause aspiration pneumonia, which is one of the most frequent causes of mortality [ 1 - 3 , 5 , 14 ].…”

Wolfram Syndrome 1 in Two Brothers Treated with Insulin Pump

“…The management of WS remains a challenge, as the progression of neurodegeneration is the primary cause of death in patients with the disease, and despite considerable efforts to improve and expand treatment options, the most effective interventions are those related to the metabolic control of diabetes. 2 , 6 A correlation has been registered between postprandial hyperglycemic peaks and the progression of the neurodegenerative course, in addition to glucose toxicity being considered an accelerating factor in the progression of the disease, besides the tissue and neuronal damage characteristic of high and sustained ER stress levels. 2 , 6 , 7 To avoid complications associated with either hypoglycemia or hyperglycemia, insulin therapy remains the first-line treatment for difficult-to-control DM; however, the method of insulin delivery has generated significant debate among health care providers.…”

“… 2 , 6 A correlation has been registered between postprandial hyperglycemic peaks and the progression of the neurodegenerative course, in addition to glucose toxicity being considered an accelerating factor in the progression of the disease, besides the tissue and neuronal damage characteristic of high and sustained ER stress levels. 2 , 6 , 7 To avoid complications associated with either hypoglycemia or hyperglycemia, insulin therapy remains the first-line treatment for difficult-to-control DM; however, the method of insulin delivery has generated significant debate among health care providers. 8 , 9 , 10 , 11 …”

“… 4 , 5 As a marker of progression, DM has garnered particular interest because it is the earliest feature to be recognized and consequently controlled; it is remarkable due to the strong correlation between metabolic control of DM, the number of associated symptoms, and the progression of neurodegenerative diseases. 5 , 6 …”

Combined MITOchondrial-NUCLEAR (MITO-NUCLEAR) Analysis for Mitochondrial Diseases Diagnosis: Validation and Implementation of a One-Step NGS Method

“…Furthermore, numerous nuclear gene mutations are also associated with MDs. Mitochondrial diseases affect preferentially tissue with high-energy demands and give rise to several degenerative disorders, involving mainly neuromuscular, ophthalmological, and gastroenterological features [1,2,[5][6][7]. In addition, deafness, diabetes, cardiomyopathy (in particular dilated, dCMP; hypertrophic, hCMP; restrictive, rCMP), and cardiac conduction defects are also frequently observed [8][9][10][11][12][13].…”