Severe metabolic disorders coexisting with Werner syndrome: a case report

Endocr J. 2021 Mar 28;68(3):261-267. doi: 10.1507/endocrj.EJ20-0448. Epub 2020 Oct 20.

Abstract

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>T:p.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delA:p.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.

Keywords: Diabetes mellitus; Progeroid; WRN gene; Werner syndrome.

Publication types

  • Case Reports

MeSH terms

  • Abortion, Habitual / physiopathology
  • Adipose Tissue / diagnostic imaging
  • Adult
  • Alopecia / physiopathology
  • Body Composition
  • Bone Diseases, Metabolic / diagnostic imaging
  • Bone Diseases, Metabolic / physiopathology*
  • Cataract / physiopathology
  • Codon, Nonsense
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Foot / etiology
  • Diabetic Foot / physiopathology
  • Fatty Liver / diagnostic imaging
  • Fatty Liver / physiopathology*
  • Female
  • Frameshift Mutation
  • Humans
  • Hypertriglyceridemia / metabolism*
  • Hypothyroidism / metabolism*
  • Hypothyroidism / physiopathology
  • Intra-Abdominal Fat / diagnostic imaging
  • Uterus / abnormalities
  • Werner Syndrome / diagnosis
  • Werner Syndrome / genetics
  • Werner Syndrome / metabolism*
  • Werner Syndrome / physiopathology
  • Werner Syndrome Helicase / genetics

Substances

  • Codon, Nonsense
  • WRN protein, human
  • Werner Syndrome Helicase