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pseudoxanthoma elasticum

Thursday 22 April 2004

Gronblad–Strandberg syndrome

Definition: Pseudoxanthoma elasticum (PXE) is a hereditary disorder of elastic tissue affecting the elastic fibers of the skin, eyes and cardiovascular system. The affected organs become progressively calcified.

It is due to a germline mutation in the MRP6/ABCC6 gene, a member of the ABC transporter family (ABCs), expressed primarily in the liver and the kidneys.

Images

- Pseudoxanthoma elasticum: Fragmented, calcium coated elastic fibers. A/w ABCC6 mut

The characteristic skin changes are asymptomatic yellow papules around the neck and in body folds giving the skin a characteristic cobblestone appearance. The eyes, cardiovascular and gastrointestinal systems are also commonly involved.

Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder characterized by calcification of elastic tissue, affecting the skin, the eyes and vascular system.

Synopsis

- vascular elastosis

  • prominent fragmentation of the internal elastic lamina
  • idiopathic arterial calcification
  • degenerated elastic fibers in the stenotic epicardial coronary arteries, the intramyocardial arterioles, the subendocardium, the mitral valve, and the blood vessels of other viscera. (10987263)
  • possible intramyocardial arteriolar involvement (10987263)

- cardiac anomalies

- coronary artery disease

  • marked coronary arterial intimal fibrosis (580722)
  • myxoid intimal fibrosis
  • endocardial lesions characterized
    • intimal fibroelastotic thickening
    • intimal fibroelastotic disorganization
    • degenerated elastic fibers
    • fragmented, calcified elastic lamina
    • fragmentation, and calcification of elastic fibers in the deeper endocardial layers
    • severe atherosclerosis
    • Fragmentation and degeneration of the elastic laminae of muscular arteries was followed by vascular calcification that could not be distinguished morphologically from Mönckeberg’s arteriosclerosis.

- diffuse intimal fibroelastotic thickening

  • intrarenal arteries (resembling that seen in hypertension)

- neurological complications (6520616)

- marked renal arterial intimal fibrosis
- possible mitral valve prolapse (mitral valve +/- myxoid) (10987263)

- cutaneous elastosis

  • disorganization of elastic fibers
  • calcification of elastic fibers
  • fragmentation of elastic fibers
  • swollen and clumped elastic fibers

Nota bene: It is important that autopsy pathologists search carefully for the pathognomonic skin lesions of PXE in cases of sudden death associated with coronary disease, mitral valve prolapse, or endocardial lesions. Recognition of this disease is essential for proper genetic counseling of surviving family members.

Etiology

- mutations in the MRP6/ABCC6 gene, a member of the ABC transporter family, expressed primarily in the liver and the kidneys.

References

- Acute myocardial infarction and a new ABCC6 mutation in a 16-year-old boy with pseudoxanthoma elasticum. Kieć-Wilk B, Surdacki A, Dembińska-Kieć A, Michalowska J, Stachura-Dereń M, Dubiel JS, Dudek D, Rakowski T, Szastak G, Bodzioch M, Aslanidis C, Schmitz G. Int J Cardiol. 2007 Mar 20;116(2):261-2. PMID: 16854481

- Varied presentations of pseudoxanthoma elasticum in a family. Sakata S, Su JC, Robertson S, Yin M, Chow C. J Paediatr Child Health. 2006 Dec;42(12):817-20. PMID: 17096720

- Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at the environment-genome interface? Uitto J, Pulkkinen L, Ringpfeil F. Trends Mol Med. 2001 Jan;7(1):13-7. PMID: 11427982

- Sudden cardiac death owing to pseudoxanthoma elasticum: a case report. Nolte KB. Hum Pathol. 2000 Aug;31(8):1002-4. PMID: 10987263

- Sudden death in pseudoxanthoma elasticum. Wilhelm K, Paver K. Med J Aust. 1972 Dec 9;2(24):1363-5. PMID: 4649999

- Fasshauer K, Reimers CD, Gnau HJ et al. Neurological complications of Gronblad–Strandberg syndrome. J Neurol 1984; 231: 250–252 (6520616)

- Mayer SA, Tatemichi TK, Spitz JL et al. Recurrent ischemic events and diffuse white matter disease in patients with pseudoxanthoma elasticum. Cerebrovasc Dis 1994; 4: 294–297 (article)

- van den Berg JS, Hennekam RC, Cruysberg JR et al. Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. Cerebrovasc Dis 2000; 10: 315–319 (10878438)

- Iqbal A, Alter M, Lee SH. Pseudoxanthoma elasticum: a review of neurological complications. Ann Neurol 1978; 4: 18–20 (697322)

- Engelman MW, Fliegelman MT. Pseudoxanthoma elasticum. Cutis. 1978 Jun;21(6):837–840. (657840)

- Pope FM. Historical evidence for the genetic heterogeneity of pseudoxanthoma elasticum. Br J Dermatol. 1975 May;92(5):493–509. [1100089]

- Navarro-Lopez F, Llorian A, Ferrer-Roca O, Betriu A, Sanz G. Restrictive cardiomyopathy in pseudoxanthoma elasticum. Chest. 1980 Jul;78(1):113–115. [7471831]

- Lebwohl MG, Distefano D, Prioleau PG, Uram M, Yannuzzi LA, Fleischmajer R. Pseudoxanthoma elasticum and mitral-valve prolapse. N Engl J Med. 1982 Jul 22;307(4):228–231. [657840]

- Mendelsohn G, Bulkley BH, Hutchins GM. Cardiovascular manifestations of Pseudoxanthoma elasticum. Arch Pathol Lab Med. 1978 Jun;102(6):298–302. [580722 ]

- CARLBORG U, EJRUP B, GRONBLAD E, LUND F. Vascular studies in pseudoxanthoma elasticum and angioid streaks; with a series of color photographs of the eyeground lesions. Acta Med Scand Suppl. 1959;350:1–84. [PubMed]

- Schachner L, Young D. Pseudoxanthoma elasticum with severe cardiovascular disease in a child. Am J Dis Child. 1974 Apr;127(4):571–575. [PubMed]

- Bete JM, Banas JS, Jr, Moran J, Pinn V, Levine HJ. Coronary artery disease in an 18 year old with pseudoxanthoma elasticum: successful surgical therapy. Am J Cardiol. 1975 Oct 6;36(4):515–520. [PubMed]

- Cunningham JR, Lippman SM, Renie WA, Francomano CA, Maumenee IH, Pyeritz RE. Pseudoxanthoma elasticum: treatment of gastrointestinal hemorrhage by arterial embolization and observations on autosomal dominant inheritance. Johns Hopkins Med J. 1980 Oct;147(4):168–173. [PubMed]