Lipoid Proteinosis 

  • Author: Kelly M Cordoro, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Nov 29, 2011
 

Background

Lipoid proteinosis is a rare autosomal recessive genodermatosis characterized by the deposition of an amorphous hyaline material in the skin, mucosa, and viscera. The classic manifestation is onset in infancy with a hoarse cry due to laryngeal infiltration. Skin and mucous membrane changes become apparent clinically, and the disease typically follows a slowly progressive, yet often benign, course. Virtually any organ may be involved, but visceral involvement rarely leads to clinically significant consequences. The exceptions are involvement of the central nervous system and respiratory tract, which may result in seizures and airway obstruction, respectively. Lifespan is otherwise normal.

Recently, lipoid proteinosis has been linked to mutations in the gene encoding extracellular matrix protein 1 (ECM1).[1, 2] To date, no effective treatment is known.

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Pathophysiology

Lipoid proteinosis is a rare genodermatosis inherited in an autosomal recessive pattern. Clinical features are myriad, and the literature describes considerable variation in severity between affected patients. Heterozygous carriers have an apparently normal phenotype but may have subtle changes such as abnormal dentition.

In 2002, loss of function mutations in the gene encoding extracellular matrix protein 1 (ECM1) on band 1q21 were identified as the cause of lipoid proteinosis.[1, 3] Frameshift and nonsense mutations have been described throughout the gene, although exons 6 and 7 seem to be the most common locations. Mutations at these particular sites appear to have genotype-phenotype relevance. Patients with exon 7 mutations display slightly milder clinical features, while mutations in exon 6 result in a more severe phenotype.

The ECM1 gene product is a glycoprotein with functional roles in skin physiology and homeostasis. ECM1 is involved in keratinocyte differentiation in the epidermis and in regulation of basement membrane integrity, interstitial collagen fibril macroassembly, and growth factor binding in the dermis. The disease is characterized by deposits of hyalinelike material in skin, mucosa, and viscera and is also referred to as hyalinosis cutis et mucosae. The original designation, lipoid proteinosis, refers to the histologic features of the deposited material, which shows similarities to both lipid and protein, although no abnormalities in lipid metabolism have been identified.

ECM1 proteins are also expressed in a number of other tissues, including the placenta, heart, liver, small intestine, lungs, ovary, testes, prostate, pancreas, kidneys, skeletal muscle, and endothelial cells. Its role in wound healing, scarring, and aging is speculated but not yet defined.

The loss of normal function of ECM1 in lipoid proteinosis is associated with a wide range of clinical abnormalities due to infiltration of the skin and viscera with hyalinelike material. The histological correlate is diffuse dermal deposition of hyaline material, basement membrane thickening at the dermoepidermal junction and around adnexa and vessels, and epidermal hyperkeratosis. These findings suggest the strong influence of ECM1 on both epidermal and dermal physiology.

The eosinophilic hyaline material is deposited in all affected organs, although whether this is a primary or secondary phenomenon is unclear. The details of the genotype-phenotype correlation regarding the nature of the hyaline deposits are currently under investigation.

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Epidemiology

Frequency

International

More than 300 cases have been reported worldwide. Incidence and prevalence figures are not available.

Mortality/Morbidity

Life span is usually normal unless altered by laryngeal obstruction or epilepsy. Patients with significant airway compromise may require permanent tracheostomy.

Race

Patients of European ancestry are most commonly affected, including South African descendants of German or Dutch immigrants. Large kindreds from South Africa have been traced back to a single German male who settled in South Africa in the 17th century.

Sex

No sex predilection is reported.

Age

Patients typically present in early childhood, but manifestations may be present at birth. Some cases may occur in adults. Adults may have subtle skin findings and may present with complications due to visceral deposition.

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Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Kelly M Cordoro, MD  Assistant Professor of Clinical Dermatology and Pediatrics, Department of Dermatology, University of California, San Francisco School of Medicine

Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Association of Professors of Dermatology, Dermatology Foundation, Medical Society of Virginia, National Psoriasis Foundation, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Michael F Osleber  University of Virginia School of Medicine

Disclosure: Nothing to disclose.

Vincent A De Leo, MD  Clinical Professor of Dermatology, Department of Dermatology, College of Physicians and Surgeons of Columbia University; Chairman, Department of Dermatology, Director of Dermatology Residency Training Program, St Luke's-Roosevelt Hospital Center; Chairman, Department of Dermatology, Beth Israel Medical Center

Vincent A De Leo, MD is a member of the following medical societies: American Academy of Dermatology, American College of Occupational and Environmental Medicine, American Contact Dermatitis Society, American Dermatological Association, American Medical Association, American Society for Photobiology, Dermatology Foundation, New York Academy of Medicine, New York County Medical Society, Photomedicine Society, Society for Investigative Dermatology, Society of Toxicology, and Women's Dermatologic Society

Disclosure: estee lauder Consulting fee Consulting; laroche posay Consulting fee Consulting; schering plough Consulting fee Consulting; pfizer Consulting fee Consulting; orfagen Grant/research funds study - clinical

Specialty Editor Board

Bernice R Krafchik, MBChB, FRCPC  Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto

Bernice R Krafchik, MBChB, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, Canadian Medical Association, College of Physicians and Surgeons of Ontario, Royal College of Physicians and Surgeons of Canada, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Lester F Libow, MD  Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor, Joseph J. Shaffer, MBBS, to the development and writing of this article.

References

  1. Hamada T, McLean WH, Ramsay M, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Hum Mol Genet. Apr 1 2002;11(7):833-40. [Medline].

  2. Hamada T, Wessagowit V, South AP, Ashton GH, Chan I, Oyama N, et al. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation. J Invest Dermatol. Mar 2003;120(3):345-50. [Medline].

  3. Nasir M, Latif A, Ajmal M, Qamar R, Naeem M, Hameed A. Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family. Diagn Pathol. Jul 26 2011;6:69. [Medline]. [Full Text].

  4. Salih MA, Abu-Amero KK, Alrasheed S, Alorainy IA, Liu L, McGrath JA, et al. Molecular and neurological characterizations of three Saudi families with lipoid proteinosis. BMC Med Genet. Feb 24 2011;12:31. [Medline]. [Full Text].

  5. Xu W, Wang L, Zhang L, Han D, Zhang L. Otolaryngological manifestations and genetic characteristics of lipoid proteinosis. Ann Otol Rhinol Laryngol. Nov 2010;119(11):767-71. [Medline].

  6. Callizo M, Ibáñez-Flores N, Laue J, Cuadrado V, Graell X, Sancho JM. Eyelid lesions in lipoid proteinosis or Urbach-Wiethe disease: case report and review of the literature. Orbit. Oct 2011;30(5):242-4. [Medline].

  7. Chan I, South AP, McGrath JA, Oyama N, Bhogal BS, Black MM, et al. Rapid diagnosis of lipoid proteinosis using an anti-extracellular matrix protein 1 (ECM1) antibody. J Dermatol Sci. Aug 2004;35(2):151-3. [Medline].

  8. Kaya TI, Kokturk A, Tursen U, Ikizoglu G, Polat A. D-penicillamine treatment for lipoid proteinosis. Pediatr Dermatol. Jul-Aug 2002;19(4):359-62. [Medline].

  9. Wong CK, Lin CS. Remarkable response of lipoid proteinosis to oral dimethyl sulphoxide. Br J Dermatol. Oct 1988;119(4):541-4. [Medline].

  10. Dowlati A, Dowlati Y, Mansauri P, et al. Lipoid proteinosis and its response to etretinate therapy. In: Pierard GE, Pierard-Franchimont C, eds. The Dermis: From Biology to Disease. Paris, France: Monographies. Dermatopathologiques Liegoises; 1989:135-42.

  11. Kroukamp G, Lehmann K. Treatment of laryngeal lipoid proteinosis using CO2 laser. S Afr Med J. Feb 2007;97(2):90, 92. [Medline].

  12. Buchan NG, Kemble JV. Successful surgical treatment of lipoid proteinosis. Br J Dermatol. May 1974;90(5):561-6. [Medline].

  13. Caccamo D, Jaen A, Telenta M, Varela E, Tiscornia O. Lipoid proteinosis of the small bowel. Arch Pathol Lab Med. May 1994;118(5):572-4. [Medline].

  14. Caplan RM. Visceral involvement in lipoid proteinosis. Arch Dermatol. Feb 1967;95(2):149-55. [Medline].

  15. Caro I. Lipoid proteinosis. Int J Dermatol. Jun 1978;17(5):388-93. [Medline].

  16. Chan I, Liu L, Hamada T, Sethuraman G, McGrath JA. The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol. Nov 2007;16(11):881-90. [Medline].

  17. Emsley RA, Paster L. Lipoid proteinosis presenting with neuropsychiatric manifestations. J Neurol Neurosurg Psychiatry. Dec 1985;48(12):1290-2. [Medline].

  18. Farolan MJ, Ronan SG, Solomon LM, Loeff DS. Lipoid proteinosis: case report. Pediatr Dermatol. Sep 1992;9(3):264-7. [Medline].

  19. Fleischmajer R, Krieg T, Dziadek M, Altchek D, Timpl R. Ultrastructure and composition of connective tissue in hyalinosis cutis et mucosae skin. J Invest Dermatol. Mar 1984;82(3):252-8. [Medline].

  20. Galadari I, Al-Kuwaiti R. Lipoid proteinosis: a case report. Int J Dermatol. May 2004;43(5):368-70. [Medline].

  21. Hofer PA. Urbach-Wiethe disease (lipoglycoproteinosis; lipoid proteinosis; hyalinosis cutis et mucosae). A review. Acta Derm Venereol Suppl (Stockh). 1973;53:1-52. [Medline].

  22. Holme SA, Lenane P, Krafchik BR. What syndrome is this? Urbach-Weithe syndrome (Lipoid proteinosis). Pediatr Dermatol. May-Jun 2005;22(3):266-7. [Medline].

  23. Hu S, Kuo TT, Hong HS. Lipoid proteinosis: report of a possible localized form on both hands and wrists. Int J Dermatol. May 2005;44(5):408-10. [Medline].

  24. Kaya TI, Tursen U, Kokturk A, Ikizoglu G, Dusmez D. The early erosive vesicular stage of lipoid proteinosis: clinical and histopathological features. Br J Dermatol. Feb 2003;148(2):380-2. [Medline].

  25. Konstantinov K, Kabakchiev P, Karchev T, Kobayasi T, Ullman S. Lipoid proteinosis. J Am Acad Dermatol. Aug 1992;27(2 Pt 2):293-7. [Medline].

  26. Kumar J, Ramesh V, Beena KR, Misra RS, Mukherjee A. Case 1: lipoid proteinosis (hyalinosis cutis et mucosae; Urbach-Wiethe disease). Clin Exp Dermatol. Sep 2002;27(6):531-2. [Medline].

  27. Moy LS, Moy RL, Matsuoka LY, Ohta A, Uitto J. Lipoid proteinosis: ultrastructural and biochemical studies. J Am Acad Dermatol. Jun 1987;16(6):1193-201. [Medline].

  28. Muda AO, Paradisi M, Angelo C, Mostaccioli S, Atzori F, Puddu P, et al. Lipoid proteinosis: clinical, histologic, and ultrastructural investigations. Cutis. Oct 1995;56(4):220-4. [Medline].

  29. Navarro C, Fachal C, Rodríguez C, Padró L, Domínguez C. Lipoid proteinosis. A biochemical and ultrastructural investigation of two new cases. Br J Dermatol. Aug 1999;141(2):326-31. [Medline].

  30. Ozbek SS, Akyar S, Turgay M. Case report: computed tomography findings in lipoid proteinosis: report of two cases. Br J Radiol. Feb 1994;67(794):207-9. [Medline].

  31. Ozkaya-Bayazit E, Ozarmagan G, Baykal C, Ulug T. [Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]. Hautarzt. Jul 1997;48(7):477-81. [Medline].

  32. Ringpfeil F. Selected disorders of connective tissue: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis. Clin Dermatol. Jan-Feb 2005;23(1):41-6. [Medline].

  33. Teive HA, Pereira ER, Zavala JA, Lange MC, de Paola L, Raskin S, et al. Generalized dystonia and striatal calcifications with lipoid proteinosis. Neurology. Dec 14 2004;63(11):2168-9. [Medline].

  34. Touart DM, Sau P. Cutaneous deposition diseases. Part I. J Am Acad Dermatol. Aug 1998;39(2 Pt 1):149-71; quiz 172-4. [Medline].

 
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Characteristic beaded papules on the eyelid (moniliform blepharosis). Courtesy of Kenneth E. Greer, MD.
Waxy, yellow skin thickening and atrophic scarring. Courtesy of Kenneth E. Greer, MD.
Beaded papules on the upper labial mucosa. Courtesy of Kenneth E. Greer, MD.
Woody induration and depression of the tongue. Courtesy of Kenneth E. Greer, MD.
Waxy, infiltrated, yellowish skin with depressed, atrophic scarring. Courtesy of Kenneth E. Greer, MD.
Waxy skin with atrophic, depressed scars on the forehead. Courtesy of Kenneth E. Greer, MD.
Infiltrated, thickened skin with atrophic and hyperpigmented scarring in 2 brothers with lipoid proteinosis. Note the tongues, which are firm and woody, ulcerated, and unable to be completely protruded because of infiltration of the frenulum. Courtesy of Kenneth E. Greer, MD.
Adult male with lipoid proteinosis. His leonine facies appearance is a result of diffuse skin infiltration. Courtesy of Kenneth E. Greer, MD.
 
 
 
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