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Clinical and Experimental Dermatology May 2024Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis, caused by mutations in the ECM1 gene. This results in the...
BACKGROUND
Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis, caused by mutations in the ECM1 gene. This results in the deposition of periodic acid-Schiff (PAS)-positive, hyaline-like material on the skin, mucosae and internal organs.
OBJECTIVES
To present a case report of LP and a systematic review to synthesize the scientific literature on the management of this uncommon and frequently missed diagnosis.
METHODS
We present a case report of a 48-year-old man with LP who exhibited significant improvement after oral acitretin therapy. To address the lack of large case-control studies on LP treatment, we performed a systematic review of the literature following the PRISMA 2020 criteria. The search was conducted in PubMed, Web of Science, Cochrane and Scopus databases from inception until June 2023. To assess the methodological quality of case reports and case series, we used the Joanna Briggs Collaboration critical appraisal tool.
RESULTS
We included 25 studies that met eligibility criteria. Data from 44 patients with a histopathologically confirmed diagnosis were analysed. Treatment ranged from systemic therapies (acitretin, etretinate, dimethyl sulfoxide, corticosteroids, penicillamine) to surgical or laser procedures. Regarding methodological quality, the main discrepancies arose in the reporting of participant characteristics and treatment interventions.
CONCLUSIONS
Low-dose oral acitretin could have potential in managing LP, exhibiting fewer side-effects compared with other therapeutic agents. Further research is needed to establish more comprehensive and evidence-based treatment guidelines.
Topics: Humans; Lipoid Proteinosis of Urbach and Wiethe; Male; Acitretin; Middle Aged; Keratolytic Agents; Treatment Outcome
PubMed: 38308656
DOI: 10.1093/ced/llae039 -
Rheumatology International Feb 2024Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder caused by an autosomal recessive mutation in the ABCC6 gene. It manifests with distinctive clinical symptoms... (Review)
Review
Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder caused by an autosomal recessive mutation in the ABCC6 gene. It manifests with distinctive clinical symptoms impacting the skin, eyes, and cardiovascular system, along with an elevated risk of cardiovascular diseases. We present a case of a 34-year-old male patient who was initially referred to the rheumatology clinic for evaluation due to suspected large vessel vasculitis. The patient's primary complaint was severe hemifacial pain radiating to the neck and upper limb. Radiological imaging studies unveiled substantial vascular narrowing and collateral vessel formation, prompting further investigation to exclude systemic vasculitis. Intriguingly, the patient also exhibited cutaneous manifestations, which were later confirmed via skin biopsy as consistent with PXE. An ophthalmological examination further revealed the presence of the classic PXE findings of angioid streaks. Given the rarity of PXE and its multifaceted clinical presentation, it can be particularly challenging to diagnose and manage. As such, cases like the one presented here may necessitate a referral to a rheumatologist for evaluation of potential systemic involvement. To provide a comprehensive perspective on PXE, we conducted a systematic review of case reports published in the past decade in English, collected from PubMed, Scopus, and the Directory of Open Access databases. The analysis of these cases will be discussed to shed light on the diversity of PXE's clinical features and the diagnostic and management dilemmas it poses and to facilitate ongoing exploration and research into this intricate condition, ultimately leading to improved care for individuals affected by PXE.
Topics: Male; Humans; Adult; Pseudoxanthoma Elasticum; Skin; Mutation; Cardiovascular System; Vasculitis; Rare Diseases
PubMed: 38141121
DOI: 10.1007/s00296-023-05509-w -
Otology & Neurotology : Official... Jul 2024To characterize the pattern of hearing loss in Charcot-Marie-Tooth (CMT) disease to help guide clinical management.
OBJECTIVE
To characterize the pattern of hearing loss in Charcot-Marie-Tooth (CMT) disease to help guide clinical management.
DATABASES REVIEWED
CINAHL, PubMed, and Scopus.
METHODS
Two independent investigators selected studies on CMT patients with pure-tone average (PTA) and auditory brainstem response (ABR) data. Case reports, case series <5 patients, and data that overlapped with another study were excluded. Investigators performed data extraction, quality rating, and risk-of-bias assessment using the Newcastle-Ottawa Scale. Meta-analysis of mean difference using fixed/random effects models was used. Also, data were analyzed using a weighted one-way analysis of variance, with post-hoc Tukey's test for comparison.
RESULTS
Ultimately, 6 prospective studies (N = 197) were included. The most common demyelinating subtype (CMT1A) had significantly prolonged ABR latency values across wave III (0.20 ms, 95% confidence interval [CI]: 0.05-0.35), wave V (0.20 ms, 95% CI: 0.01-0.39), waves I-III (0.20 ms, 95% CI: 0.01-0.39), and waves I-V (0.20 ms, 95% CI: 0.01-0.39) when compared to matched controls. The autosomal recessive demyelinating subtype (CMT4C) had significantly worse PTA when compared to the most common subtype (CMT1A) (Δ 28.93 dB, 95% CI 18.34-39.52) and nondemyelinating subtype (CMT2A) (Δ 28.3 dB, 95% CI: 15.98-40.62).
CONCLUSIONS
Patients with CMT can present with a variety of phenotypes depending on the causative mutation. The ABR interpeak latency values for the most common demyelinating form of CMT are delayed when compared to matched controls. Most subtypes have normal hearing thresholds, apart from CMT4C, which presents with mild hearing loss on average.
PubMed: 38956759
DOI: 10.1097/MAO.0000000000004243 -
Frontiers in Endocrinology 2023Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The...
Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The disease is caused by a heterozygous activating mutation of the calcium-sensing receptor () gene, encoding a G-Protein-coupled cell membrane sensor of extracellular calcium concentration mainly expressed by parathyroid glands, renal tubules, and the brain. ADH1 has been linked to 113 unique germline mutations, of which nearly 96% are missense mutations. There is often a lack of a clear genotype/phenotype correlation in the reported literature. Here, we described a case series of 6 unrelated ADH1 probands, each one bearing a gain-of-function mutation, and two children of one of these cases, matching our identified mutations to the same ones previously reported in the literature, and comparing the clinical and biochemical characteristics, as well as the complication profile. As a result of these genetic and clinical comparisons, we propose that a genotype/phenotype correlation may exist because our cases showed similar presentation, characteristics, and severity, with respect to published cases with the same or similar mutations. We also contend that the severity of the presentation is highly influenced by the specific variant. These findings, however, require further evaluation and assessment with a systematic review.
Topics: Gain of Function Mutation; Receptors, Calcium-Sensing; Calcium; Research; Mutation
PubMed: 37654565
DOI: 10.3389/fendo.2023.1215036 -
Molecular Medicine Reports Feb 2024Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of...
Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole‑exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co‑segregation analysis was conducted. A frameshift mutation in (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by early‑onset hypertension and hypokalemia. The mutation led to the truncation of the β subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of follow‑up data from patients with Liddle syndrome with mutations was performed. The follow‑up data of 108 patients with pathogenic mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and early‑onset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Frameshift Mutation; Mutation; Hypertension; Potassium
PubMed: 38099339
DOI: 10.3892/mmr.2023.13142