LAUSR

Lipoid proteinosis autosomal recessive multisystem disorder -was first described in 1929 by Urbach (dermatologist), and Wiethe (ear, nose, and throat specialist). Until date up to 300 cases have been reported in the English literature (1–4). The disease is presented by dermatologic, laryngeal, ophthalmologic, and neurological manifestations, and is thought to be associated with the mutation in ‘Extracellular Matrix Protein-1ʹ (ECM-1 protein) in chromosome 1q21 (2,3). The syndrome is characterized by accumulation of amorphous hyaline material in the skin, mucosa and the internal organs, and characterized by a hoarse voice from the infancy (4). Herein we report ocular manifestations of lipoid proteinosis due to a genetic mutation in ECM1 gene. A 43-year-old male presented with the complaint of bilateral itching in both eyes for many years. On detailed ophthalmological examination, best corrected visual acuity was 20/20 in both eyes, anterior segment examination revealed yellowwhite beaded papules on both superior and inferior lid margins which are typical for moniliform blepharosis (Figure 1(a)). Anterior segment optic coherence tomography, meibography and Scheimpflug camera (Pentacam, Oculus, Wetzlar, Germany) imaging were performed (Figure 1(b–f)). Rest of the ophthalmologic examination was normal. Systemic examination revealed large scattered brown lesions at the thoracal and genital areas and extremities (Figure 1(g)). There were multiple, grouped; about 3–5 mm sized lesions at elbows resembling the eyelid lesions (Figure 1(h)). The patient had a hoarse voice since early childhood. There is not any presence of parental consanguinity or involvement in other family members. Biochemical and hematological blood sampling were within normal limits. Biopsy of the eyelid lesions was consistent with the histopathological diagnosis of lipoid proteinosis (Figure 1(j–l). The psychiatry examination revealed anger attacks and sertraline (Lustral, Pfizer, Turkey) 50 mg once a day and risperidone (Risperdal, Johnson&Johnson, Turkey) 1 mg once a day a quarter were initiated. Sequencing analysis revealed a homozygous c. G879A (p.S293S) mutation in ECM1 gene (Figure 1(i)). This unique mutation was described before by Gao D et al (5). It is generally unexpected to find a pathogenic synonymous variant in the middle of a coding exon. But it was clearly shown that this synonymous variant generated a cryptic splice site and it might result in a truncated protein (5). Lipoid proteinosis is an autosomal recessive disease; characterized by the accumulation of hyaline, amorphous, eosinophilic material in the skin. Hoarseness of the voice in early childhood is typical. (1-7) Pale brown-yellow spot-like skin lesions may occur in the face, extremities, head skin and internal organs in later ages, additionally multiple bulging lesions might be detected on the elbow, knee and eyelids. (2,4) In some cases, anger attacks, paranoia, long-term memory weakness and temporal lobe epilepsy were reported. (6) In the presented case anger attacks that required treatment were diagnosed. Although ocular findings in lipoid proteinosis are identified since the first description of the disease, they are not observed in every patient. Moniliform blepharosis and accumulation pattern of the eyelids are characteristic and accumulations can be seen in clinical practice on other ocular surfaces such as cornea and conjunctiva (7). Classical ocular involvement of the syndrome – moniliform blepharosis – is observed as yellow-white beaded papules on the edge of the eyelids. This ocular involvement – as in the present patient – has a high diagnostic sensitivity. Other ocular involvements of the syndrome include infiltration of Meibomian, Zeiss and Moll glands, madarosis, trichiasis, macular degeneration, and Bruch’s membranes drusenoid formation (7). Less common ocular involvements are glaucoma, which may develop due to accumulation of hyaline material in the trabecular meshwork; lens pathologies such as cataract, subluxation or dislocation; pathologies associated with retinal deposition; corneal pathologies such as keratoconus, opacities, ulceration; uveitis and nasolacrimal duct obstruction (7). None of these possible ocular findings were detected in the present patient expect moniliform blepharosis and increased central corneal thickness in both eyes. It was demonstrated that the disease is related to extracellular matrix protein 1 gene (ECM1) (8). In 2013 c.G879A mutation in ECM1 gene was reported in compound heterozygous state in a patient (5). For the first time in the literature this uniquemutation