When Wolfram syndrome is caused by mutations in the WFS1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Some studies have shown that people who carry one copy of a WFS1 gene mutation are at increased risk of developing individual features of Wolfram syndrome or related features, such as type 2 diabetes, hearing loss, or psychiatric illness. However, other studies have found no increased risk in these individuals.

Most patients with Wolfram syndrome have diabetes mellitus and bladder dysfunction in combination with diabetes insipidus. The dose escalation of desmopressin for the treatment of diabetes insipidus should be carefully done because demopressin may cause hyponatremia. If the sodium in your blood is too low, you have a condition called hyponatremia. You need some sodium in your bloodstream to control how much water is in and around the cells in your body. As a result of low sodium, the amount of water in your body rises and causes your cells to swell. This can lead to many different problems. Some of them are mild. Others can be serious and even life-threatening. Hyponatremia is a common clinical problem in patients with Wolfram syndrome that requires careful management.

Headache may be related to autonomic dysfunction or neuropathy. Some patients experience sharp and stabbing unilateral pain similar to trigeminal neuralgia. A consultation with a neurologist is recommended. Carbamazepine or amitriptyline has been shown to be effective in some patients.

Autonomic neuropathy is commonly seen in patients with Wolfram syndrome. Signs and symptoms include orthostatic hypotension, anhidrosis, hypohidrosis, hyperhidrosis, constipation, gastroparesis, hypothermia, and hyperpyrexia. A thorough history and review of systems may reveal most of these complaints. Gastrointestinal conditions can be managed by changes in diet, small frequent meals, increased fiber diet, and increased water intake.

Wolfram syndrome is characterized by progressive neurodegeneration. The most common problem is ataxia. Cerebellar ataxia should be assessed yearly or twice a year by neurologists. Dysarthria and swallowing disorders (dysphagia) are commonly seen. Swallowing treatment by a speech-language pathologist is beneficial for patients to prevent aspiration pneumonia. Surgical procedures, including esophageal dilation and esophagomyotomy, have been shown to be effective in some patients. Oral hygiene and dental care are important because dysphagia may lead to the impaired clearance of organisms and pathogenic colonization.