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Lipoid proteinosis (LP) is a rare genodermatosis characterized clinically by mucocutaneous lesions, hoarseness developing in early childhood and, at times, neurological complications.
ORPHA:530Classification level: Disorder
Incidence and prevalence are not known. More than 300 cases (ages 6 to 67 years) have been reported worldwide. Most patients are of European ancestry (Dutch or German). A founder effect is reported among large kindreds in South Africa. Many cases are also reported from the Middle East and India. The disease is more commonly seen in consanguineous unions.
A wide range of clinical signs is noted and disease severity is variable, while the course is usually slowly progressive. The usual presenting manifestation is a hoarse cry due to laryngeal infiltration at birth or in infancy. Subsequently, skin and mucous membrane changes develop in the first two years of life. Crusted lesions initially appear on the face and extremities and heal with scarring. Waxy, thickened and at times verrucous skin lesions may affect the face, eyelids, axillae, knees and scrotum. Eyelid beading (moniliform blepharosis) is a hallmark feature but occurs later in childhood. Patchy or diffuse hair loss may be present. The oral mucosa is often involved with cobblestone lips, tongue or gingiva, impaired tongue mobility causing speech problems, and transient swelling and ulceration of the lips and tongue. Oligodontia (see this term) may be present. Respiratory tract infiltration may cause upper respiratory tract infections, hoarseness or aphonia, dysphagia, and airway obstruction. Dystonia, seizures, behavioral changes, learning difficulties and short stature have been reported in affected children. Less commonly, the disease manifests in adulthood with subtle skin findings and possible complications due to visceral deposition. Heterozygous carriers are generally asymptomatic but may have a mild presentation including abnormal dentition.
LP is caused by deposition of an amorphous hyaline material in the skin, mucosa, and viscera. Causative loss-of-function mutations have been found in the ECM1 gene (1q21) encoding extracellular matrix protein 1, which has a role in physiology and homeostasis of the skin and many other tissues.
Diagnosis is based on the clinical signs (particularly hoarseness and skin manifestations). Histological findings on biopsy of affected cutaneous or mucosal sites show periodic acid-Schiff-positive deposition of amorphous hyaline material in the papillary dermis which confirms the diagnosis. Cranial magnetic resonance imaging or computed tomography reveals bean-shaped intracerebral calcifications in the temporal lobe (in up to 75% of patients). Molecular genetic testing confirms the diagnosis.
The main differential diagnoses are hydroa vacciniforme and autosomal erythropoietic protoporphyria, but also include leprosy, lichen amyloidosis (see these terms), and xanthomas.
If a family member is affected by the disease and the gene mutation has been confirmed, prenatal diagnosis is possible.
LP is inherited in an autosomal recessive manner. Genetic counseling should be provided to affected families.
Management and treatment
There is currently no known effective curative treatment and no standard treatment approach. D-penicillamine, oral dimethyl sulfoxide, acitretin, topical corticosteroids, and carbon dioxide laser have been used with varying degrees of success. Treatment of LP with acitretin has shown some efficacy for hoarseness after use over a long period, but there has been variable success in treating the skin lesions.
The prognosis is generally favorable. Fatal outcomes are uncommon, but the disease may strongly impact quality of life.