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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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
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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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