RESUMEN
PURPOSE: Lipoid proteinosis (LP) or Urbach-Wiethe disease (OMIM 247100) is a rare syndrome characterised by early vocal folds infiltration and subsequent multi-organ involvement. LP is often unrecognised and its associated hoarseness is overlooked. The main objective of the study was to investigate hoarseness in LP and implement a diagnosis among otolaryngologists. METHODS: PubMed/MEDLINE and OMIM databases were systematically searched. Authors concentrated the search on published articles starting from the discovery of the pathogenesis of LP by Hamada et al. in 2002. Only cases in which a diagnosis was reported both clinically and through biopsy and/or genetic molecular testing were included. Characteristics of the LP cases were extracted from each included study. Results were obtained through Generalized Estimating Equations. RESULTS: The search strategy yielded 217 articles, of which 74 (34.1%) met the selection criteria. A total of 154 cases were included. Hoarseness was described in all LP cases and clearly stated as the onset symptom in 68.8%. The onset was on average at 19 months of age (CI: 3.00-20.00), while the mean age at diagnosis was 15 years (CI: 10.00-30.00). Therefore, the diagnostic delay amounted to 13.42 years (CI: 8.00-23.83). Hoarseness alone was responsible for an LP diagnosis in only 14.3% of cases. In 43.5% of cases, genetic analysis of the ECM1 gene was performed and exon 6 was the most frequently altered portion. CONCLUSION: Analysing the largest number of published cases, the study underlined that hoarseness is the key symptom for diagnosing LP since early childhood, though frequently overlooked.
Asunto(s)
Ronquera , Proteinosis Lipoidea de Urbach y Wiethe , Proteinosis Lipoidea de Urbach y Wiethe/genética , Proteinosis Lipoidea de Urbach y Wiethe/diagnóstico , Proteinosis Lipoidea de Urbach y Wiethe/patología , Humanos , Ronquera/etiología , Niño , Femenino , Preescolar , Masculino , Adolescente , Lactante , Proteínas de la Matriz ExtracelularRESUMEN
Abstract Lipoid proteinosis is a rare autosomal recessive disease, characterized by hyaline deposits of PAS-positive material in tissues due to mutations in the ECM1 gene. This study evaluated the ultrastructure of the skin of a 6-year-old child affected by this condition. The light microscopy identified PAS-positive hyaline deposits, which were more intense in the papillary dermis. Scanning electron microscopy of the dermis showed a compact papillary dermis and fibrillar deposits in the middle dermis. Transmission electron microscopy clearly showed the deposition of fibrillar material in the dermis, forming clusters adherent to elastic fibers, between the collagen bundles and the collagen fibers, and also filling up the cytoplasm of dermal fibroblasts.
Asunto(s)
Humanos , Niño , Proteinosis Lipoidea de Urbach y Wiethe , Piel , Proteínas de la Matriz Extracelular , Colágeno , Hialina , MicroscopíaRESUMEN
Lipoid proteinosis is a rare autosomal recessive disease, characterized by hyaline deposits of PAS-positive material in tissues due to mutations in the ECM1 gene. This study evaluated the ultrastructure of the skin of a 6-year-old child affected by this condition. The light microscopy identified PAS-positive hyaline deposits, which were more intense in the papillary dermis. Scanning electron microscopy of the dermis showed a compact papillary dermis and fibrillar deposits in the middle dermis. Transmission electron microscopy clearly showed the deposition of fibrillar material in the dermis, forming clusters adherent to elastic fibers, between the collagen bundles and the collagen fibers, and also filling up the cytoplasm of dermal fibroblasts.
Asunto(s)
Proteinosis Lipoidea de Urbach y Wiethe , Niño , Colágeno , Proteínas de la Matriz Extracelular , Humanos , Hialina , Microscopía , PielRESUMEN
BACKGROUND: Lipoid proteinosis is a rare autosomal recessive disorder caused by mutations in the extracellular matrix protein 1 gene. It is characterised by deposition of hyaline material in the skin and mucous membranes. This paper describes the management of two cases with laryngopharyngeal disease. METHODS: Two patients with a biopsy diagnosis of lipoid proteinosis were identified from the surgical pathology archive covering the period 2004-2016. Their notes were reviewed. RESULTS: An adult male and an adult female were identified. Both had dysphonia and laryngopharyngeal lesions. The patients underwent interval laser microlaryngoscopy to debulk disease but minimise mucosal injury and scarring, using a 'pepper pot' technique. Both had adequate symptom control. CONCLUSION: Lipoid proteinosis is a rare genetic condition, which typically presents in infancy with dysphonia and subsequent skin involvement. Two cases are presented to demonstrate that laryngotracheal symptoms can be controlled with interval laser debulking and the 'pepper pot' technique without causing stenosis.
Asunto(s)
Hipofaringe/patología , Hipofaringe/cirugía , Laringoscopía , Proteinosis Lipoidea de Urbach y Wiethe/patología , Proteinosis Lipoidea de Urbach y Wiethe/cirugía , Adulto , Diagnóstico Diferencial , Disfonía/etiología , Femenino , Ronquera/etiología , Humanos , Hialina , Terapia por Láser/métodos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Resultado del TratamientoRESUMEN
Objective To report a family with lipoid proteinosis (LP) from Shandong province and to analyze mutations in the extracellular matrix protein 1 (ECM1) gene in this family.Methods Eight members in a threegeneration family with LP were clinically investigated,and two patients were identified to suffer from LP,including the proband (Ⅲ 1) and her mother (Ⅱ 2).Both of the patients presented with papules on the palpebral margin,short and thick lingual frenum,and hoarseness.Indirect laryngoscopy showed infiltrating and thickening of the vocal cord.Pathological examination of lesions on the palpebral margin and laryngeal mucosa revealed deposits of hyaline-like material in the dermis,which was strongly positive for periodic acid-Schiff (PAS) staining and resistant to diastase digestion.The pathological diagnosis was LP.Blood samples were collected from all the family members and 100 ethnically matched,unrelated and unaffected Chinese human controls followed by DNA extraction.PCR and sequencing were performed to detect the ECM1 gene,and nested PCR followed by agarose gel electrophoresis to analyze mutations in the coding region of the ECM1 gene.Results Both of the two patients were compound heterozygotes.Three missense mutations,incluing p.P169T,p.A44T and p.R392W,were found in the ECM1 gene of the affected mother,with p.P169T in one allele and p.A44T as well as p.R392W in the other.The girl patient inheried the missence mutation p.P169T from her mother and a synonymous mutation c.879G ＞ A from her father (Ⅱ 1).Nested PCR showed that the c.978G ＞ A mutation generated a splice-acceptor site AG,which leaded to a splicing defect.Conclusion A novel synonymous splice-acceptor site mutation c.879G ＞ A in the ECM1 gene is identified in the family with LP.
RESUMEN
A síndrome de Urbach-Wiethe, também conhecida como lipoidoproteinose ou hialinose cutânea e mucosa (OMIM 247100), é rara genodermatose de herança autossômica recessiva, de patogênese desconhecida, que se caracteriza pela deposição de material hialino na pele, mucosa oral e órgãos internos. Alterações características incluem a rouquidão, pápulas e nódulos na face, especialmente na borda das pálpebras, cicatrizes varioliformes, espessamento difuso e aspecto amarelado da pele e lesões verrucosas em áreas de atrito.
Urbach-Wiethe disease, also named lipoproteinosis or hyalinosis cutis et mucosae (OMIM 247100), is a rare autosomal recessive disorder of unknown pathogenesis with hyaline-like material deposition in the skin, oral mucosa and internal organs. Typical features include hoarseness, papules and nodules on the face, characteristically along the eyelid margins, pitted scars, diffuse thickening and yellow discoloration of the skin, and verrucous lesions in areas subjected to trauma.
RESUMEN
Apresentação de um caso de síndrome de Urbach-Wiethe com manifestações típicas, inclusive oculares. Paciente do sexo feminino, 15 anos, com quadro de prurido ocular relacionado à presença de lesões papuliformes em margens palpebrais (blefarose moniliforme), em associação com outras alterações sistêmicas. O diagnóstico foi confirmado por meio de biópsia cutânea e foi instituído uso de lágrimas artificiais, com alívio parcial do sintoma. O objetivo do trabalho é relatar um caso com manifestações características da doença atendido no Setor de Oftalmologia da Faculdade de Medicina de Marília.
We present a case of Urbach-Wiethe syndrome with typical findings, including ocular lesions. A 15-year-old girl was referred to our department complaining of itchy eyelid lesions (moniliform blepharosis) associated with other systemic manifestations. Diagnosis was confirmed by performing skin biopsy. Artificial tears were prescribed, with partial relief of the symptom. The objective of the present study is to describe a typical case of Urbach-Wiethe syndrome attended at the Ophthalmologic Sector of the Medical School of Marília.