Urbach-Wiethe Research Articles

Neurobiological Effects of Lipoid Proteinosis: A Study on Phosphorylated Tau, S100B, NSE, NEFL, and GFAP

Background: Lipoid Proteinosis (LP), also termed Urbach-Wiethe disease, is an enigmatic genodermato-sis marked by the systemic deposition of hyaline material. With its etiology rooted in ECM1 mutations, LP’s neuropathological spectrum has been hypothesized to involve an array of neurodegenerative biomarkers, underscoring a potential for substantial neurobiological implications. This study endeav-ored to elucidate the serum concentrations of neurodegenerative biomarkers—phosphorylated Tau (pMAPT), S100B, Neuron-Specific Enolase (NSE), Neurofilament Light Chain (NEFL), and Glial Fibrillary Acidic Protein (GFAP)—in LP patients, seeking to establish their diagnostic utility for the condition. Materials and Methods: Fifteen LP patients and 15 matched healthy controls were enrolled. Serum levels of the biomarkers were quantified using ELISA, and their predictive power was assessed through binary logistic regression and Receiver Operating Characteristic (ROC) analysis. Results: Elevated serum levels of NSE, NEFL, and GFAP were observed in LP subjects relative to healthy counterparts, reaching statistical significance (p<0.05). In contrast, pMAPT and S100B levels did not differ appreciably. GFAP is considered a predictive marker for LP with an area under the curve (AUC) value of 0.813 and a 95% confidence interval (CI) of 0.658-0.968 (p=0.003). Conclusions: The study underscores a distinctive neurodegenerative profile in LP, with NSE, NEFL, and GFAP concentrations significantly amplified. These biomarkers, particularly GFAP, may represent novel indicators for LP, offering prospective biomarker-based diagnostic strategies. The insights garnered herein pave the way for advanced understanding and clinical management of LP, delineating a novel avenue for future high-impact research.

Laryngeal features in Lipoid proteinosis: a systematic review and meta-analysis of individual participant data.

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. 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. 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 19months of age (CI: 3.00-20.00), while the mean age at diagnosis was 15years (CI: 10.00-30.00). Therefore, the diagnostic delay amounted to 13.42years (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. 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.

Eponyms that honor Jewish dermatologists: A celebration and a remembrance, Part three: Jewish physicians who practiced during the Holocaust and in its aftermath

Part III of this contribution continues to celebrate the many contributions that Jewish physicians have made to advance the specialty of dermatology, as reflected by eponyms that honor their names. Part I covered the years before 1933, a highly productive period of creativity by Jewish dermatologists, especially in Germany and Austria. The lives of 17 Jewish physicians and their eponyms were described in Part I. Part II focused on the years of 1933 to 1945, when the Nazis rose to power in Europe, and how their anti-Semitic genocidal policies affected leading Jewish dermatologists caught within the Third Reich. Fourteen Jewish physicians and their eponyms are discussed in Part II. Part III continues the remembrance of the Holocaust era by looking at the careers and eponyms of an additional 13 Jewish physicians who contributed to dermatology during the period of 1933 to 1945. Two of these 13 physicians, pathologist Ludwig Pick (1868-1944) and neurologist Arthur Simons (1877-1942), perished in the Holocaust. They are remembered by the following eponyms of interest to dermatologists: Lubarsch-Pick syndrome, Niemann-Pick disease, and Barraquer-Simons syndrome. Four of the 13 Jewish physicians escaped the Nazis: Felix Pinkus (1868-1947), Herman Pinkus (1905-1985), Arnault Tzanck (1886-1954), and Erich Urbach (1893-1946). Eponyms that honor their names include nitidus Pinkus, fibroepithelioma of Pinkus, Tzanck test, Urbach-Wiethe disease, Urbach-Koningstein technique, Oppenheim-Urbach disease, and extracellular cholesterinosis of Karl-Urbach. The other seven Jewish physicians lived outside the reach of the Nazis, in either Canada, the United States, or Israel. Their eponyms are discussed in this contribution. Part III also discusses eponyms that honor seven contemporary Jewish dermatologists who practiced dermatology after 1945 and who continue the nearly 200 years of Jewish contribution to the development of the specialty. They are A. Bernard Ackerman (1936-2008), Irwin M. Braverman, Sarah Brenner, Israel Chanarin, Maurice L. Dorfman, Dan Lipsker, and Ronni Wolf. Their eponyms are Ackerman syndrome, Braverman sign, Brenner sign, Chanarin-Dorfman syndrome, Lipsker criteria of the Schnitzler syndrome, and Wolf's isotopic response.

New onset dyspnea and stridor in an adolescent with Urbach-Wiethe disease.

New onset dyspnea and stridor in an adolescent with Urbach-Wiethe disease.

A clinical case of Urbach-Wiethe disease

A clinical description of Urbach – Wiethe disease (lipoid proteinosis), an extremely rare pathology, is presented, currently only 300 cases are known. This hereditary disease, transmitted by an autosomal recessive type, is associated with a mutation of the extracellular matrix 1 (ECM1) gene located on chromosome 1, locus 1q21. It is based on a violation of collagen synthesis and deposition of hyaline in the dermis along the collagen fibers, in the mucous membranes, sometimes in the internal organs. The chemical composition of hyaline is not completely determined; it is noted that it includes collagen, glycoproteins, lipids, proteoglycans. The disease begins in early childhood and is characterized by changes in the ENT organs and skin, confirmed by histological examination, which reveals thickening of the dermis, degeneration of collagen fibers, hyalinosis with deposition around the vessels, in their walls, around the sweat glands of ribbon-like, weakly eosinophilic, homogeneous substances, which include phospholipids, sometimes there may be cracks with deposition of lipids.
 Patient V., born in 1990, the disease began almost from birth with the appearance of polymorphic rashes on the skin and hoarseness of the voice. In 1999, a histological examination of the affected skin was performed, confirming the diagnosis of lipoid proteinosis of Urbach – Wiethe. The skin pathological process is widespread, symmetrical, on the face it is represented by reticulated telangiectatic erythema, along the edge of the lower eyelids there are miliary nodules similar to a string of pearls. Hypoplasia and stagnant erythema of the auricles are determined. There are yellowish lenticular papules on the trunk and limbs, waxy translucent plaques of a dense consistency in the area of the extensor surface of the elbow joints. Besides, secondary hyperpigmentation and foci of atrophy were detected on the face, trunk and limbs. Skin changes are accompanied by lesion of the ENT organs in the form of bilateral maxillary sinusitis, frontitis, chronic pharyngitis, chronic laryngitis. Concomitant pathology is important: polyvalent sensitization, chronic hepatitis B, biliary dyskinesia against the background of gallbladder deformation, chronic gastroduodenitis. The patient has been on disability since 2000, needs dispensary supervision and correction of all identified violations.

Lipoid Proteinosis, Its Symptoms, and Oral Manifestations: A Case Report and Review of Literature

Introduction: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is an autosomal recessive disorder characterized by the deposition of glycoproteins in mucous membranes, skin, and organs. Symptoms typically begin in childhood, persist throughout life, and encompass hoarseness, skin inflammation, scarring, and ulcers, resulting in a waxy appearance. Oral manifestations present as white plaques and ulcers, significantly impacting the oral cavity. To date, approximately 400 cases have been reported worldwide. Case Presentation: Herein, we present the case of a 36-year-old female diagnosed with LP who sought a dental implant evaluation. Her medical history revealed tooth decay, which necessitated extractions, and she had previously undergone maxillary implant placement and mandibular bone grafting. Upon general examination, the patient exhibited voice hoarseness, hyperkeratosis on the elbows and hands, and papules on the fingers. Oral examination revealed firm and fibrotic mucosa, papillomatosis, and limited mouth opening. Hyposalivation and the absence of the left parotid duct orifice were noted. No significant abnormalities were observed on the eyelids or face. Salivary gland assessment indicated a reduced flow rate (1 ml in 5 minutes). This case highlights the importance of conducting a comprehensive evaluation and tailoring management strategies to the individual needs of patients with LP. Conclusions: Lipoid proteinosis is a rare mucocutaneous disorder characterized by a slow and benign course, with varying prevalence in different regions. Early recognition of oral symptoms is crucial, as they often precede skin and neurological manifestations. Although typical oral signs usually include tongue firmness and an inability to protrude, these were not observed in the present case. Xerostomia and dental agenesis, though uncommon, have been reported in previous cases, consistent with the findings of the present case, although different areas of the oral cavity might be involved in some instances.

Eye involvement in lipoid proteinosis: A rare clinically forgotten entity

Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis having multisystem syndromic involvement of skin, upper aerodigestive tract, internal organs, and eyelids. Although the ocular manifestations are rare, it is important to identify these clinical entities for early diagnosis and improved outcomes. We, hereby, describe a case of a 17-year-old female who presented with complaints of chronic itching and discomfort of both eyelids on and off.

Urbach-Wiethe disease: a rare pediatric case report

Urbach-Wiethe disease also known as lipoid proteinosis (LP) is a rare autosomal recessive Geno dermatosis.1 It is characterized by the deposition of an amorphous hyaline material in the skin, mucosa and viscera and is also known as cutaneous-mucosal hyalinosis.2,3 Parental consanguinities is identified in approximately 20% of Urbach-Wiethe disease cases. The classic manifestation due to laryngeal infiltration is a hoarse cry with its onset in infancy. Skin and mucous membrane changes become clinically apparent important consequences.4 Rarely, the central nervous system and respiratory tract may be involved resulting in seizures and airway obstruction, respectively. The lifespan is generally normal. We report a case of Urbach-Wiethe disease in a 6-year-old boy with hoarseness of voice who was started on oral acitretin therapy following his diagnosis. Oral acitretin can prove useful in cases of lipoid proteinosis who present with hoarseness of voice or vocal cord palsy. The mutations in the gene encoding extracellular matrix protein 1 (ECM1) have been linked to lipoid proteinosis. Even though no effective treatment is known, acitretin has proved to reverse hoarseness of voice in few reported cases and was started in our case as it was his chief presenting complaint.

Urbach-Wiethe disease in a young patient without apparent amygdala calcification

Urbach-Wiethe disease is an extremely rare genetically-based syndrome which usually leads to dermatological and neurological changes. Neurologically, the amygdaloid region is primarily bilaterally affected. Therefore, several functions modulated by the amygdala are changed in patients with Urbach-Wiethe disease. As the neurological alterations evolve only gradually, it is particularly important to determine the cognitive and brain status of a juvenile. The patient described here was seen briefly at age 9 and tested neuropsychologically at age 19; furthermore, computer tomography and magnetic resonance imaging of his head was done. There were no important abnormalities in the brain, which is unusual in the light of previous data from other patients. On the cognitive level, the patient was generally within normal limits. However, he had mild problems in attention and concentration, and more prominent problems in emotional processing domain, and in personality dimensions. It is concluded that amygdala calcifications in Urbach-Wiethe disease take place progressively-possibly underpinned by genetic and gender variables; this can subsequently allow psychosocial-social factors (such a proper education and socialization) and biological factors (compensatory neuroplasticity) to retard and diminish the development of socio-emotional and cognitive deteriorations, though the outcome of questionnaires indicates that such patients may develop substantial concerns as to their future life and well-being.

Lipoid Proteinosis Due to Homozygous Nonsense Mutation in Extracellular Matrix Protein 1 (ECM1) Gene in Three Pakistani Siblings

Introduction Urbach–Wiethe disease (or lipoid proteinosis) is an autosomal recessive genetic disease. It is caused by a mutation in the extracellular matrix protein 1 gene (ECM1), resulting in deposition of hyaline material at the dermoepidermal junction of the skin, around blood vessels, and at multiple other sites. Case presentation The present report describes three siblings born to nonconsanguineous parents who presented with hoarseness, macroglossia, yellow waxy skin, beaded papules on the eyelids, atrophic scars, and recurrent skin infections. Histopathologic examination showed hyaline deposition at the interface between the dermis and epidermis and at the basal lamina of blood vessels. Exome sequencing revealed a homozygous nonsense variant in ECM1. This variant created a premature stop codon, leading to loss of function. Both parents were heterozygous for the same mutation. Conclusion This report is a useful addition to the current knowledge base regarding this phenotypically and genetically variable genodermatosis, which is rarely reported in Pakistan.

Assessment of dynamic thiol-disulfide homeostasis in patients with lipoid proteinosis (Urbach-Wiethe syndrome).

SUMMARYOBJECTIVE:Lipoid proteinosis is a rare autosomal recessive genetic dermatological disease that occurs due to the accumulation of hyaline material in the skin and mucous membranes. This study aimed to investigate whether dynamic thiol-disulfide homeostasis is a new marker of oxidative stress in patients suffering from lipoid proteinosis.METHODS:The study group involved 17 patients with lipoid proteinosis and 17 healthy controls with same gender and age. Native thiol, total thiol, disulfide levels, and thiol-disulfide indexes were measured with the fully automated spectrophotometric method described by Erel and Neselioglu, and the results of the two groups were statistically analyzed.RESULTS:Serum total thiol and native thiol levels were significantly lower in lipoid proteinosis group compared to the control group (p=0.020 and p=0.014, respectively). The disulfide levels were found to be higher in lipoid proteinosis group, but there was no significant difference between two groups.CONCLUSIONS:Impaired dynamic thiol-disulfide homeostasis was observed in lipoid proteinosis patients, suggesting that thiol-disulfide homeostasis may have a role in the pathogenesis of this disease.

TOO MUCH OF NOT ENOUGH: Exploring Lack of Fear and Its Consequences

IntroductionFear is an unpleasant emotional response to perceiving a threat causing physiological changes. Humans feel fear for positive motives, as it plays a crucial role in our survival. Just as the right balance in life is ideal, pathological fear is often described in one of its exaggerations, of having too much. However, lack of fear or “hypophobia” can be just as devastating and debilitating. This can be demonstrated in the analogy between those who feel no pain who also demonstrate increased risk and decreased life expectancy.ObjectivesThe authors aim to explore the concept of fear, discussing currently known physiological mechanisms in order to explain the effects that alterations of these mechanisms can have on fear responses, namely lack of fear, and subsequently the consequence of this on mental health.MethodsA brief non-systematized literature review was performed based on works most pertinent to the topic discussed.ResultsMuted fear responses have been mentioned in the literature, principally associated with medical conditions affecting the physiological fear pathways, including Urbach-Wiethe disease. Amygdala damage provokes abnormal fear reactions and reduced fear experience. This appears to be similar to what is seen in psychopathy, where abnormalities in the limbic system produce abnormal fear responses.ConclusionsAny extreme can cause havoc on a well-balanced machine. Just as the excess of fear results in mental issues such as anxiety, a lack of fear can also be debilitating. Those demonstrating less fear could help investigators better understand mental health disorders that have been demonstrated to be mediated by similar processes.DisclosureNo significant relationships.

An Unusual Pigmented Plaque in a Newborn.

An Unusual Pigmented Plaque in a Newborn.

A case of Urbach-Wiethe disease associated with ictal fear (4474)

A case of Urbach-Wiethe disease associated with ictal fear (4474)

Lipoid Proteinosis (Urbach-Wiethe Disease): A Rare Genodermatosis with Characteristic Dermatological and Neuroimaging Findings.

Lipoid Proteinosis (Urbach-Wiethe Disease): A Rare Genodermatosis with Characteristic Dermatological and Neuroimaging Findings.

Urbach–wiethe disease: Hyalinosis cutis et mucosae

Urbach-Wiethe Disease is an uncommon entity with autosomal recessive inheritance. We describe the clinical and histopathological findings of lipoid proteinosis in this clinical image. Cicatricial alopecia, atrophic scar on face, moniliform blepharosis and alopecia are the characteristic features of this disease entity. Hoarseness of voice and seizure can also be seen in these patients. Skin biopsy confirms the diagnosis. Multidisciplinary involvement is recommended for the management of these cases.

Anaesthetic considerations in a child with Urbach Wiethe disease posted for removal of cheek swelling.

Anaesthetic considerations in a child with Urbach Wiethe disease posted for removal of cheek swelling.

Urbach–Wiethe disease - Case report

Urbach–Wiethe disease - Case report

A Protective Mechanism against Illusory Perceptions Is Amygdala-Dependent.

Most people have a clear sense of body ownership, preserving them from physical harm. However, perceptual body illusions - famously the rubber hand illusion (RHI) - can be elicited experimentally in healthy individuals. We hypothesize that the amygdala, a core component of neural circuits of threat processing, is involved in protective mechanisms against disturbed body perceptions. To test this hypothesis, we started by investigating two monozygotic human twin sisters with focal bilateral amygdala damage due to Urbach-Wiethe disease. Relative to 20 healthy women, the twins exhibited, on two occasions 1 year apart, augmented RHI responses in form of faster illusion onset and increased vividness ratings. Following up on these findings, we conducted a volumetric brain morphometry study involving an independent, gender-mixed sample of 57 healthy human volunteers (36 female, 21 male). Our results revealed a positive correlation between amygdala volume and RHI onset, i.e., the smaller the amygdala, the less time it took the RHI to emerge. This raised the question of whether a similar phenotype would result from experimental amygdala inhibition. To dampen amygdala reactivity, we intranasally administered the peptide hormone oxytocin to the same 57 individuals in a randomized trial before conducting the RHI. Compared with placebo, oxytocin treatment yielded enhanced RHI responses, again evident in accelerated illusion onset and increased vividness ratings. Together, the present series of experiments provides converging evidence for the amygdala's unprecedented role in reducing susceptibility to the RHI, thus protecting the organism from the potentially fatal threats of a distorted bodily self.SIGNIFICANCE STATEMENT Compelling evidence indicates that the amygdala is of vital importance for danger detection and fear processing. However, lethal threats can arise not only from menacing external stimuli but also from distortions in bodily self-perception. Intriguingly, the amygdala's modulatory role in such illusory body perceptions is still elusive. To probe the amygdala's involvement in illusory body experiences, we conducted a multi-methodological series of experiments in a rare human amygdala lesion model, complemented by a morphological and pharmaco-modulatory experiment in healthy volunteers. Our findings convergently suggest that the amygdala's integrity is indispensable for maintaining an unbiased, precise perception of our bodily self. Hence, the amygdala might shield us against distortions in self-perception and the resultant loss of behavioral control of our organism.

Lipoid proteinosis and epilepsy: Molecular analysis

Aim: Lipoid proteinosis (LP) is also known as Urbach-Wiethe disease which is a rare autosomal recessive disorder characterized by intracellular accumulation of hyaline material in skin and mucosae. LP has typical neurological, dermatological and radiological findings. The pathogenesis of disease is unknown. In literature several cases have been reported up to date. Mutations in extracellular matrix protein 1 (ECM1) gene have been found to cause the disease. We evaluated the molecular features of a family diagnosed with LP and evaluate the known and novel mutations of LP. Material and Methods: Genomic DNA was extracted from peripheral blood of the patients and family members including clinically normal parents and two siblings of the two affected subjects by using a commercial DNA extraction kit. Polymerase chain reaction was performed for all 10 exons of ECM1 gene by using the primers defined. Results: All of the exons of the ECM1 gene were sequenced and this revealed a 2-bp deletion in exon 7 of the ECM1 gene in both patients and both parents. Patients have the homozygous 2-bp deletions (c735del TG) and the parents and two healthy siblings showed heterozygous 2-bp deletion. Conclusions: Our patients found to be homozygous for the deletion in ECM1 gene. In order to understand the molecular pathology of the disease in detail, further functional analysis of the mutations should be performed.