DISEASE CARD

Disease group Connective tissue disorders
DISEASE NAME LIPOID PROTEINOSIS
Synonymous Urbach-Wiethe disease; Lipoproteinosis; Hyalinosis cutis et mucosae
Estimated prevalence Unknown (over 250 reported cases)
OMIM 247100
Inheritance Autosomal recessive
Gene (s) ECM1 (602201)

Definition

Lipoid proteinosis (LP) is an autosomal recessive condition characterized by progressive deposition of hyaline material in the skin, mouth, upper respiratory tract and other internal organs. Its main clinical features are thickening of the vocal cords with a hoarse voice, followed by skin thickening with waxy papules and varicelliform or acneiform scar formation

Clinical Description

The first clinical symptom of LP is hoarseness of voice secondary to thickening of the vocal cords. Skin lesions usually manifest during the first years of life, but may appear later. They are mainly localized to the face and extremities and consist in yellowish, waxy papules/plaques and skin thickening, along with vesicles and scars. Beaded papules on the eyelid margins (moniliform blepharosis) are a characteristic finding. Diffuse skin thickening and infiltration gradually develops over time and can be accentuated by warty hyperkeratosis, in particular on extensor surfaces. Vesicles and blisters and, less frequently, pustules healing with crusts and scars are most prominent during childhood. Varicelliform or acneiform scars, sometimes reported to occur spontaneously, are a constant finding. Mild alopecia is described in some patients. Mucosal thickening is evident on buccal mucosa, tongue and frenulum, pharynx and larynx, occasionally leading to dysphagia and respiratory insufficiency. Seizures and psychiatric disorders are possible neurological complications.

Pathogenesis

LP is due to recessive mutation of the ECM1 gene, encoding for the extracellular matrix protein 1. Its functions in skin biology are still not completely understood, although a role in regulating skin vessel homeostasis has been proposed. In particular, inefficient draining of fluids and macromolecules due to the lack of cutaneous lymphatic vessels may lead to the accumulation of protein-rich material in the extracellular matrix. A further hypothesis suggests that defective ECM1 protein could lead to altered protein binding, perhaps to basement membrane proteins or associated macromolecules. This could result in accumulation of collagen IV and other non-collagenous proteins that may account for the hyaline material deposition in the skin and other tissues.

Diagnosis

The diagnosis of LP is suspected on clinical grounds (i.e. hoarse voice and characteristic skin and mucosal lesions). Histopathologic examination of a lesional skin biopsy confirms the diagnosis, showing dermal vessels and appendages surrounded by PAS-positive, diastase-resistant, thickened basement membrane and focal deposition of hyaline material in the dermis. Electron microscopy reveals thickening and reduplication of the basement membrane around blood vessels, appendages, smooth muscle cells, nerve endings and beneath the epithelium. Cytoplasmic vacuole formation in dermal fibroblasts and abnormal lysosomes with curved tubular profiles in dermal eccrine glands and histiocytes have also been described. Mutational screening of the ECM1 gene represents the ultimate confirmation of the diagnosis.

Treatment

Cutaneous lesions may partially improve with dimethyl sulfoxide, etretinate, surgical and carbon dioxide laser procedures. Mucosal stripping and laser surgery may be helpful to treat thickening of the vocal cords. Tracheostomy may be required in case of respiratory insufficiency.