Diabetes mellitus coexisted with progeria: a case report of atypical Werner syndrome with novel LMNA mutations and literature review

Abstract

Werner syndrome (WS) is a rare, adult-onset progeroid syndrome. Classic WS is caused by WRN mutation and partial atypical WS (AWS) is caused by LMNA mutation. A 19-year-old female patient with irregular menstruation and hyperglycemia was admitted. Physical examination revealed characteristic faces of progeria, graying and thinning of the hair scalp, thinner and atrophic skin over the hands and feet, as well as lipoatrophy of the extremities, undeveloped breasts at Tanner stage 3, and short stature. The patient also suffered from severe insulin-resistant diabetes mellitus, hyperlipidemia, fatty liver, and polycystic ovarian morphology. Possible WS was considered and both WRN and LMNA genes were analyzed. A novel missense mutation p.L140Q (c.419T>A) in the LMNA gene was identified and confirmed the diagnosis of AWS. Her father was a carrier of the same mutation. We carried out therapy for lowering blood glucose and lipid and improving insulin resistance, et al. The fasting glucose, postprandial glucose and triglyceride level was improved after treatment for 9 days. Literature review of AWS was performed to identify characteristics of the disease. Diabetes mellitus is one of the clinical manifestations of WS and attention must give to the differential diagnosis. Gene analysis is critical in the diagnosis of WS. According to the literature, classic and atypical WS differ in incidence, pathogenic gene, and clinical manifestations. Characteristic dermatological pathology may be significantly more important for the initial identification of AWS. Early detection, appropriate treatments, and regular follow-up may improve prognosis and survival of WS patients.

Severe metabolic disorders coexisting with Werner syndrome: a case report

“…[15]. We used "Werner syndrome" and "WRN mutation", "Werner syndrome" and "LMNA mutation", "Werner syndrome" or "progeria" to search in English database (Pubmed), and Chinese database (China National Knowledge Infrastructure (CNKI) up to 15th August 2020, and found 16 Chinese patients with WS reported [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Demographic (i.e., age, sex) and clinical characteristics of individual patients were summarized in Table 2. WS was accurately diagnosed in the patient through the collection of a detailed medical history, a careful physical examination, and obtaining extensive laboratory test results.…”

Early Onset Diabetes in Two Children due to Progeria, a Monogenic Disease of DNA Repair

“…Only in WS, the adult form of progeria syndrome, diabetes mellitus due to severe insulin resistance has been reported as a possible clinical manifestation. The possible mechanism of insulin resistance includes reduced insulin receptors in fat cells, loss of signal transduction after the binding of normal insulin to normal receptors and a defective post-receptor step ( 1 ). In addition, dysregulation of adipocytokine may be another mechanism for the development of diabetes mellitus in WS patients.…”

“…Less is known about metabolic complications in children with progeria syndrome. In WS, also known as adult progeroid syndrome, type 2 like diabetes mellitus is one of the clinical manifestations of the disease and attention must give to the differential diagnosis ( 1 ).…”

The Possible Role of Β-Cell Senescence in the Development of Type 2 Diabetes Mellitus

“…There is every reason to believe that beta-cells senescence and associated consequences may have some genetic basis. Indeed, diabetes mellitus was reported to co-exist with progeria [113]. Progeria (premature aging) or Werner syndrome (WS), also known as adult progeroid syndrome, is a rare, early-onset, and age-related disease characterized by segments of aging phenotypes [113].…”

“…Indeed, diabetes mellitus was reported to co-exist with progeria [113]. Progeria (premature aging) or Werner syndrome (WS), also known as adult progeroid syndrome, is a rare, early-onset, and age-related disease characterized by segments of aging phenotypes [113]. In addition, it was shown that partial lipodystrophy with severe insulin resistance may manifest in WS-linked premature aging syndrome [114].…”