1-O-Alkylglycerol accumulation reveals abnormal ether glycerolipid metabolism in Sjögren-Larsson syndrome.

Sjögren-Larsson syndrome (SLS) is an inherited metabolic disease characterized by ichthyosis, spasticity, intellectual disability and deficient oxidation and accumulation of of fatty aldehydes and alcohols. We investigated whether excess fatty alcohols in SLS are diverted into biosynthesis of ether glycerolipids (eGLs) by measuring the 1-O-alkylglycerol (AG) backbone of eGLs in stratum corneum, plasma and red blood cells (RBCs). In all tissues, saturated and monounsaturated AGs were detected. In stratum corneum from SLS patients, saturated AGs (C15-C20) were increased 97-fold (range: 86- to 169-fold) compared to controls. AGs were largely (67 ± 9%) derived from neutral esterified eGLs (i.e. alkyl-diacylglyerol) and free non-esterified AGs (28 ± 10%), but very little from plasmalogens (3 ± 5%). Plasma from SLS patients had 2-fold more C18:0-AG (p < 0.005) and 40% less C16:1-AG (p < 0.01) than controls but the total concentration of AGs was not increased, and the AG profile in RBCs from SLS subjects was normal. All AGs were profoundly reduced in plasma and RBCs from patients with Zellweger spectrum disorder, who have impaired eGL (i.e. plasmalogen) synthesis. The striking accumulation of AGs in stratum corneum of SLS patients constitutes a novel lipid biomarker for this disease, and may contribute to the pathogenesis of the ichthyosis. Measurement of AGs is a simple and convenient method to assess global synthesis of eGLs and potentially identify patients with defects in their metabolism.

Late-Stage Sjögren-Larsson Syndrome Maculopathy Imaged With OCT Angiography.

Three adult siblings with Sjögren-Larsson syndrome (SLS) demonstrated signs of late-stage SLS maculopathy, including intraretinal crystals, atrophic changes, and lipofuscin deposition. This first report of SLS maculopathy imaged with optical coherence tomography angiography revealed decreased retinal capillary density, vessel dilation, and increased flow voids in the superficial and deep capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e78-e82.].

Intrathecal Baclofen Therapy for the Treatment of Spasticity in Sjögren-Larsson Syndrome.

Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjögren-Larsson syndrome who had pump implantation for intrathecal baclofen. We observed a positive response, with a decrease of spasticity, reflecting in the Modified Ashworth Scale, and parents and caregivers observed a functional improvement in both patients. One patient experienced skin irritation 15 months after surgery, necessitating pump repositioning. No infection occurred. Our report shows that intrathecal baclofen therapy can have a positive therapeutic effect on spasticity in patients with Sjögren-Larsson syndrome, and therefore may be a promising addition to current treatments.

Unusual presentation Of Sjögren-associated neuropathy with plasma cell-rich infiltrate.

INTRODUCTION: Sjögren syndrome is thought to be a lymphocyte-driven process. Peripheral nervous system involvement occurs in about 20%-25% of patients. A sensory-predominant, large-fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation. METHODS: We report a rare case of an acute Sjögren-associated, sensory predominant, length-dependent peripheral neuropathy mimicking Guillain-Barré syndrome. The patient presented with sensory ataxia preceded by fever and polyarthralgia. She gave a history of years of dry eyes and dry mouth. RESULTS: She had a positive Shirmer test, abnormal salivary gland scan, and positive SS-A and SS-B antibodies. A sural nerve biopsy showed an unusual, dense, non-IgG4, polyclonal, plasma-cell perivascular infiltrate. The patient responded to treatment with weekly pulse intravenous methylprednisolone. CONCLUSIONS: Sjögren syndrome can present with acute-onset, sensory predominant peripheral neuropathy. The role of plasma cells in Sjögren syndrome is unexplored and deserves further study. Muscle Nerve 55: 605-608, 2017.

Ocular manifestations of genetic skin disorders.

Genetic skin diseases, or genodermatoses, often have extracutaneous manifestations. Ocular manifestations in particular can have significant clinical implications, like blindness. Other manifestations, such as the corneal opacities that occur in X-linked ichthyosis, are asymptomatic but characteristic of a particular genodermatosis. Ophthalmologic examination can aid in diagnosis when characteristic findings are seen. The genodermatoses with ocular manifestations will be reviewed, but neurocutaneous, syndromes, genetic pigmentary disorders, and genetic metabolic diseases are not included because they are covered elsewhere in this issue.

Síndrome Sjögren - Larsson / Sjögren - Larsson syndrome

Relatam-se os casos de dois irmãos consanguíneos com síndrome de Sjögren- Larsson, enfatizando a importância clínica do exame oftalmológico. BPLS, masculino, 11 anos e MBLS, feminino, 10 anos, irmãos de pais não-consanguíneos, apresentando ictiose congênita, diplegia espástica e retardo mental. Ao exame oftalmológico, apresentavam miopia, fotofobia, baixa acuidade visual. A fundoscopia, presença de cristais branco-amarelados em área foveal e parafoveal em ambos os olhos. Aconselhamento genético foi realizado. O manejo foi de suporte. A Síndrome de Sjögren-Larsson é uma rara doença autossômica recessiva em que há 100 por cento de penetrância. Síndrome de Sjögren-Larsson é classicamente caracterizada por ictiose, espasticidade e deficiência mental. A doença é causada por mutações no gene aldeído desidrogenase. As alterações oculares observadas são geralmente bilaterais, cristais branco-amarelados em área retiniana, que aparecem nos dois primeiros anos de vida e que vão aumentando em número com a idade. As anormalidades oculares não têm relação com a severidade da ictiose ou com as anormalidades neurológicas. Acredita-se que as lesões oftalmológicas sejam um sinal patognomônico da síndrome. É necessário enfatizar a importância do diagnóstico precoce e possibilidades de tratamento dietético.

Sjogren - Larsson syndrome is a rare autosomal recessively inherited neurocutaneous disorder which occurs with 100 percent penetrance and is classically characterized by ichthyosis, spasticity and mental handicap. The disease is caused by mutations in the aldehyde dehydrogenase gene. The ocular manifestations are highly characteristic bilateral, glistening yellow-white retinal dots from the age of 1 to 2 years onward. The number of dots increases whit age. The extent of the macular abnormality does not correlate with the severity of the ichthyosis or with the severity of the neurological abnormalities. We report the clinical characteristics and ocular manifestations associated with the Sjögren-Larsson syndrome in two siblings, emphasizing the clinical importance of the ophthalmological examination of the Sjögren-Larsson syndrome. BPLS, a eleven year old boy and MPLS, a ten year old girl from non-consanguinous parents, presenting congenital ichthyosis, spastic diplegia and mental retardation. Miopia, fotofobia, subnormal visual acuity and glistening yellow-white crystalline deposits that were located in the foveal and parafoveal area were found in the ophthalmologic examination.

Lymphocytic mastitis preceding Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and B cell hyperreactivity. Lacrimal and salivary glands are the most commonly involved causing keratoconjunctivitis sicca and xerostomia. A wide variety of other glandular and extraglandular manifestations can occur in SS. Lymphocytic mastitis is a rare presentation of several conditions including diabetes mellitus and autoimmune disorders. We report a case of a 43-year-old woman with a four-year history of arthralgias and positive antinuclear antibodies who developed a right painless breast mass. Biopsy revealed lymphocytic mastitis with predominant B cells. One year later she developed severe constitutional symptoms, sicca symptoms, lymphadenopathy, anemia, and interstitial lung disease. Serologies and minor salivary gland were consistent with the diagnosis of SS. This case further supports the association of lymphocytic mastitis with autoimmune diseases and demonstrates that it can even precede the clinical diagnosis of these entities.

Distrofia macular cristalina em paciente com síndrome de Sjögren-Larsson: relato de caso / Macular crystalline dystrophy in Sjögren-Larsson syndrome: case report

Apresentação de um caso de distrofia macular cristalina em paciente do sexo feminino com síndrome de Sjögren-Larsson. A doença caracteriza-se pela tríade: ictiose congênita, diplegia ou tetraplegia espástica e retardo mental. Os olhos são acometidos em até 100% dos casos sendo característica a presença de maculopatia cristalina como observado na paciente relatada. À fundoscopia observou-se a presença de depósitos esbranquiçados perifoveais. A tomografia de coerência óptica evidenciou pontos hiper-reflexivos correspondentes aos depósitos intrarretinianos, atrofia macular com redução na espessura macular em ambos os olhos. Os achados relacionados à síndrome, à tomografia de coerência óptica foram apresentados de maneira inédita em nosso meio.

Presentation of a case of crystalline macular distrophy diagnosed in a female patient with Sjögren-Larsson syndrome. The disease consists of clinical findings of spastic diplegia or tetraplegia, mental retardation, and congential ichthyosis. The eyes are affected in up to 100% of cases, and crystalline maculopathy is the main finding as described in this case report. On fundus examination multiple white dots were observed at ophthalmoscopy. The optical coherence tomography has shown not only the hipereflexive intraretinal spots but also macular atrophy with macular thickness reduction. The tomographic findings were first described in our country.

Subclinical changes in the juvenile crystalline macular dystrophy in Sjögren-Larsson syndrome detected by optical coherence tomography.

PURPOSE: To study morphologic changes in the macula by optical coherence tomography (OCT) in patients with a crystalline macular dystrophy due to the autosomal recessive neurocutaneous Sjögren-Larsson syndrome (SLS). DESIGN: Retrospective observational case series. PARTICIPANTS: Twenty-seven eyes of 14 patients, mean age 14.6 (range, 3-24) years, with biochemically and genetically proven SLS underwent clinical and OCT investigation between September 2004 and September 2006. METHODS: All patients underwent full ophthalmologic examination including slit-lamp biomicroscopy and binocular ophthalmoscopy. Optical coherence tomography of all eyes was performed using the macular thickness map protocol of Stratus OCT. MAIN OUTCOME MEASURES: Macular morphology in clinical examination and OCT. RESULTS: Beside clinically visible perimacular crystalline deposits in all eyes of all study participants, macular morphology and reflectivity were significantly changed on OCT compared with healthy eyes. We found focal hyperreflectivities in all study eyes within the perifoveal ganglion cell layer and the inner plexiform layer, corresponding to the clinical localization of retinal crystals. More interestingly, a cystoid foveal degeneration on OCT was present in the majority of patients with SLS (18/27 eyes, or 67% of all eyes studied), varying from multiple microcystoid spaces to cystoid foveal atrophy. In general, patients who were severely affected on OCT showed intense changes on previously performed cerebral magnetic resonance spectroscopy. CONCLUSIONS: Patients with SLS show a childhood-onset crystalline macular dystrophy with cystoid foveal atrophy on OCT in most cases. The intraretinal deposition of lipid metabolites may lead to Müller cell degeneration with subsequent formation of cystoid spaces or atrophic changes within the fovea. Because this macular dystrophy is present in all examined patients with SLS, familiarity with this maculopathy seems important for the diagnosis of this rare systemic disease.

Gluten sensitivity in patients with primary Sjögren's syndrome.

OBJECTIVE: To evaluate the rectal mucosal response to gluten as an indication of gluten sensitivity in patients with primary Sjögren's syndrome (pSS). MATERIAL AND METHODS: Rectal challenges with wheat gluten were performed in 20 patients with pSS and 18 healthy control subjects. Fifteen hours after challenge the mucosal production of nitric oxide (NO) was measured. RESULTS: Five patients with pSS had a significant increase in the luminal release of NO after the rectal gluten challenge, indicating gluten sensitivity. All were HLA-DQ2 and/or -DQ8-positive. Two of the patients with increased NO had antibodies against transglutaminase and a duodenal biopsy showed an absolutely flat mucosa consistent with coeliac disease in one of the patients. Before gluten challenge, 15 of the Sjögren's syndrome (SS) patients reported gastrointestinal symptoms, and 8 reported intolerance to various food products. No correlation was found between gluten sensitivity and self-reported food intolerance or gastrointestinal symptoms. CONCLUSIONS: Rectal mucosal inflammatory response after gluten challenge is often seen in patients with pSS, signifying gluten sensitivity. However, this reactivity is not necessarily linked to coeliac disease.

[Sjögren's syndrome: clinical and therapeutic features. A review of the literature]. / La sindrome di Sjgren: aspetti clinici e terapeutici. Revisione della letteratura.

UNLABELLED: Sjögren' Syndrome (SS), also named Sicca Syndrome, is a complex disease, characterized by a series of clinical symptoms and signs chiefly represented by xerostomia, xerophthalmia and connectival diseases. The pathogenetic mechanisms consist of an autoimmune process leading to salivary and lacrimal glands progressive destruction. There is a primary form with salivary and lacrimal glands compromission only and a second form in which xerostomia and/or xerophthalmia are associated with connectival diseases like rheumatoid arthritis, systemic lupus erythematosus and scleroderma. The diagnosis of SS is rather difficult and it is based on various world-wide established and accepted criteria: the labial minor salivary glands biopsy and the research of specific seric autoantibodies are the basic elements. From the therapeutic point of view, various types of immunomodulant treatments based on cyclosporine, corticosteroids, methotrexate or alpha-interferon have been proposed with different RESULTS: Cholinergic drugs, like pilocarpine and cevimeline, are also used in order to stimulate the gland functionality.

Esclerodermia o esclerosis sistemica. A proposito de un caso / Esclerodermia or Sistemic Esclerosis. A propos of a case

Aprocechando el caso de una niña que se presento en el Hospital Daniel Bracamonte de la ciudad de Potosi, se describe la enfermedad que engloba a un grupo de enfermedades que pertenecen al grupo de las colagenosis. La esclerodermia (del griego esclero.dura y dermia-piel) es uan enfermedad rara de naturaleza autoinmune y todas ellas tienen como sintomas comunes el endurecimiento de la piel y adelgazamiento cutaneo: La esclerosis sistemica no solo afecta al sistema autoinmune sino a la pared de los vasos sanguineos y el tejido conectivo

Sjögren-Larsson syndrome: case reports.

Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder with worldwide distribution. It consists of ichthyosis, spastic diplegia, and mental retardation. An enzymatic defect in fatty alcohol oxidation recently was identified and is thought to be responsible for the disorder. We report two siblings with SLS. In addition to the typical features of the syndrome, the sister had marked hyperkeratosis of the palms and soles, which is rarely seen to this degree. The brother had joint hyperextensibility, which has not been reported previously. Both individuals had documented deficient activity of fatty alcohol:NAD+ oxidoreductase.