Werner syndrome (WS), also known as adult progeria, is a rare autosomal hereditary progeroid disorder with highly heterogeneous clinical manifestations. The variable phenotype frequently causes delayed diagnosis or misdiagnosis. Metabolic disease is common in WS: diabetes mellitus affects about 55% of affected individuals and can be mistaken for type 1 or type 2 diabetes because of overlapping metabolic features. Accurate etiologic diagnosis matters because management strategies and prognostic considerations differ when diabetes is secondary to an underlying monogenic or syndromic disorder.
A 50-year-old man presented to the First Affiliated Hospital of Xinjiang Medical University in September 2024 with poorly controlled diabetes. Clinical findings reported included diabetes mellitus and hyperlipidemia alongside physical features suggestive of premature aging: hoarseness and atrophy of subcutaneous fat and muscles in the face and limbs. A relevant family history detail was parental consanguinity, which raised the pretest probability of a recessive inherited disorder in this patient.
Because of the constellation of premature-aging features and metabolic disease, genetic sequencing was performed. Testing identified a homozygous mutation in the WRN gene: c.1846G>C, resulting in the amino acid substitution p.Ala616Pro. The presence of a homozygous WRN pathogenic change established the diagnosis of Werner syndrome in this patient and explained the clinical syndrome that had previously been attributed to routine type 2 diabetes.
Following genetic confirmation of WS, the treating team reclassified the patient’s diabetes as a specific form of monogenic diabetes associated with the underlying Werner syndrome, rather than conventional type 2 diabetes. The authors reported that an individualized precision treatment plan was developed based on the etiologic diagnosis. The source did not provide detailed elements of that precision treatment plan or specific therapeutic agents or dosing changes; those details were not reported in the abstract.
This case underscores the diagnostic challenges when common metabolic presentations occur in the context of a rare hereditary syndrome. Key clinical signals prompting genetic evaluation included: premature-aging phenotypic features (facial and limb subcutaneous fat and muscle atrophy, hoarseness), metabolic disease poorly controlled by standard therapies, and a family history consistent with autosomal recessive inheritance (parental consanguinity).
Genetic confirmation of a pathogenic WRN variant changed the diagnostic classification from typical type 2 diabetes to monogenic diabetes secondary to WS, allowing clinicians to pursue precision medicine approaches tailored to the genetic etiology. The report emphasizes that genetic testing can prevent misdiagnosis as type 1 or type 2 diabetes and can inform individualized management strategies that may improve glycemic control and overall outcomes for patients with WS.
Clinicians evaluating adults with atypical diabetes presentations or signs of premature aging should maintain a low threshold for genetic consultation and testing, as identifying an underlying syndrome such as Werner syndrome can materially change diagnostic classification and management strategy.