-
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 -
Nephron Feb 2024Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition, however its relationship with renal cell carcinoma (RCC) remains unclear. This...
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition, however its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients.
METHODS
A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed.
RESULTS
Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1 to 5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7 to 7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9 to 56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7 to 95.1, I2 = 66.9%]).
CONCLUSION
ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however may become apparent as outcomes and life expectancy amongst APDKD patients improve.
PubMed: 38301614
DOI: 10.1159/000536245 -
Clinical and Experimental Medicine Jan 2024Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of...
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma, and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants in PIK3CD and PIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function variants in the PIK3CD gene, while loss of function variants in PIK3R1 have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. Despite available treatments, survival for individuals with APDS appears to be shortened from the average lifespan. A Kaplan-Meier survival analysis for APDS showed the conditional survival rate at the age of 20 years was 87%, age of 30 years was 74%, and ages of 40 and 50 years were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The overall mortality rate for HSCT in APDS1 and APDS2 cases was 15.6%, while the mortality rate for lymphoma was 47.6%. This survival and mortality data illustrate that new treatments are needed to mitigate the risk of death from lymphoma and other cancers as well as infection. These analyses based on real-world evidence gathered from the medical literature comprise the largest study of survival and mortality for APDS to date.
Topics: Adult; Humans; Young Adult; Class I Phosphatidylinositol 3-Kinases; Immunologic Deficiency Syndromes; Lymphoma; Mutation; Neoplasms; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Primary Immunodeficiency Diseases; Survival Rate; Middle Aged
PubMed: 38280023
DOI: 10.1007/s10238-023-01259-y -
PharmacoEconomics - Open Mar 2024Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to iron overload and multiorgan failure.
BACKGROUND
Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to iron overload and multiorgan failure.
OBJECTIVES
The aim of this systematic review was to provide up-to-date evidence of all the current data on the costs and cost effectiveness of screening and treatment for HH.
METHODS
We searched PubMed, Cochrane Library, National Health Service Economic Evaluation Database (NHSEED), Cost-Effectiveness Analysis Registry (CEA Registry), Health Technology Assessment Database (HTAD), Centre for Reviews and Dissemination (CRD), and Econlit until April 2023 with no date restrictions. Articles that reported cost-utility, cost-description, cost-minimization, cost-effectiveness, or cost-benefit analyses for any kind of management (drugs, screening, etc.) were included in the study. Patients with HH, their siblings, or individuals suspected of having HH were included in the study. All screening and treatment strategies were included. Two authors assessed the quality of evidence related to screening (either phenotype or genotype screening) and treatment (phlebotomy and electrophoresis). Narrative synthesis was used to analyse the similarities and differences between the respective studies.
RESULTS
Thirty-nine papers were included in this study. The majority of the studies reported both the cost of phenotype screening, including transferrin saturation (TS), serum ferritin, and liver biopsy, and the cost of genotype screening (HFE screening, C282Y mutation). Few studies reported the cost for phlebotomy and erythrocytapheresis treatment. Data revealed that either phenotype or genotype screening were cost effective compared with no screening. Treatment studies concluded that erythrocytapheresis might be a cost-effective therapy compared with phlebotomy.
CONCLUSIONS
Economic studies on either the screening, or treatment strategy for HH patients should be performed in more countries. We suggest that cost-effectiveness studies on the role of deferasirox in HH should be carried out as an alternative therapy to phlebotomy.
PubMed: 38279979
DOI: 10.1007/s41669-023-00463-6 -
International Journal of Molecular... Jan 2024Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.
Topics: Humans; Cardiomyopathy, Hypertrophic; Genetic Testing; Arrhythmias, Cardiac; Autopsy; Fibrosis; Phenotype; Death, Sudden, Cardiac
PubMed: 38279275
DOI: 10.3390/ijms25021275 -
American Journal of Speech-language... Mar 2024This systematic review represents an update to previous reviews of the literature addressing behavioral management of respiratory/phonatory dysfunction in individuals...
PURPOSE
This systematic review represents an update to previous reviews of the literature addressing behavioral management of respiratory/phonatory dysfunction in individuals with dysarthria due to neurodegenerative disease.
METHOD
Multiple electronic database searches and hand searches of prominent speech-language pathology journals were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards.
RESULTS
The search yielded 1,525 articles, from which 88 met inclusion criteria and were reviewed by two blinded co-investigators. A large range of therapeutic approaches have been added to the evidence base since the last review, including expiratory muscle strength training, singing, and computer- and device-driven programs, as well as a variety of treatment modalities, including teletherapy. Evidence for treatment in several different population groups-including cerebellar ataxia, myotonic dystrophy, autosomal recessive spastic ataxia of Charlevoix-Saguenay, Huntington's disease, multiple system atrophy, and Lewy body dementia-were added to the current review. Synthesis of evidence quality provided strong evidence in support of only one behavioral intervention: Lee Silverman Voice Treatment Program (LSVT LOUD) in people with Parkinson's disease. No other treatment approach or population included in this review demonstrated more than limited evidence, reflecting that these approaches/populations require urgent further examination.
CONCLUSION
Suggestions about where future research efforts could be significantly strengthened and how clinicians can apply research findings to their practice are provided.
SUPPLEMENTAL MATERIAL
https://doi.org/10.23641/asha.24964473.
Topics: Humans; Neurodegenerative Diseases; Dysarthria; Speech Therapy; Voice Training; Parkinson Disease
PubMed: 38232176
DOI: 10.1044/2023_AJSLP-23-00274 -
Epilepsia Mar 2024KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a...
OBJECTIVE
KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.
METHODS
Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.
RESULTS
Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).
SIGNIFICANCE
This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Young Adult; Electroencephalography; Epilepsies, Myoclonic; Myoclonic Epilepsies, Progressive; Potassium Channels; Seizures; Unverricht-Lundborg Syndrome
PubMed: 38231304
DOI: 10.1111/epi.17880 -
Journal of Neurology May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by...
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.
METHODS
A retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.
RESULTS
Ten cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).
CONCLUSIONS
ICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.
Topics: Humans; CADASIL; Cerebral Hemorrhage; Middle Aged; Male; Prevalence; Risk Factors; Female; Aged; Adult; Retrospective Studies
PubMed: 38217707
DOI: 10.1007/s00415-023-12177-0 -
European Review For Medical and... Dec 2023A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis. (Meta-Analysis)
Meta-Analysis
Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.
OBJECTIVE
A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis.
MATERIALS AND METHODS
We reviewed and examined scientific articles from PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane from the initiation date till June 2023 to identify investigations that examined metformin performance in managing ADPKD. Among the employed search terminology, we searched for terms such as "metformin" and "ADPKD". MA was conducted using the Cochrane Collaboration's RevMan version 5.3.0 (The Cochrane Collaboration, Oxford, UK).
RESULTS
We identified 4 investigations, with 164 total subjects who fulfilled our inclusion criteria. The experimental cohort displayed a marked reduction in the decline of estimated glomerular filtration rate (eGFR) relative to controls [mean difference (MD) = 2.31, 95% confidence interval (CI) = 0.82-3.79, p = 0.002]. We observed no obvious difference in the height-adjusted total kidney volume alteration, gastrointestinal side effects, and hypoglycemia between the two cohorts.
CONCLUSIONS
Metformin was easily tolerable and safe and substantially reduced the eGFR decline among ADPKD patients. Moreover, although metformin-treated patients were more likely to suffer gastrointestinal adverse events, we observed no discernible difference between the two cohorts.
Topics: Humans; Polycystic Kidney, Autosomal Dominant; Glomerular Filtration Rate; Metformin; Disease Progression; Kidney
PubMed: 38164854
DOI: 10.26355/eurrev_202312_34789 -
Bone Mar 2024Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The physiological mechanism for the development of NF1-related bone abnormal turnover is still unclear.
OBJECTIVES
A meta-analysis was performed to investigate the effects of NF1 on bone mineral density (BMD) and osseous metabolic indices in order to provide clinical evidence for the pathogenesis of the associated skeletal deformities.
METHODS
A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed/Medline and Web of Science databases from the date of inception of each database through to 10 September 2023. Specific inclusion and exclusion criteria were applied for the identification of studies examining the effects of NF1 on bone strength and metabolism. The Newcastle-Ottawa and Jadad scales were applied to assess the quality of the included studies. RevMan 5.3 software was used for the analysis of the data, and MedCalc was applied to examine publication bias.
RESULTS
Overall, 13 studies met the inclusion criteria comprised of 5 cross-sectional, 6 case-control and 2 retrospective studies. 703 patients and 973 healthy subjects formed the NF1 and control group, respectively. The results of the meta-analysis displayed that lumbar (SMD = -3.85, 95%CI = -7.53 to -0.18, Z = 2.05, p = 0.04) and femoral (SMD = -4.78, 95%CI = -8.86 to -0.69, Z = 2.29, p = 0.02) BMD was reduced in the NF1 group. Both in children and adults the serum levels of 25 hydroxyvitamin D3 were also decreased in NF1 group, but without any statistical significance (SMD = -0.62, 95%CI = -1.34 to -0.11, Z = 1.66, p = 0.10). Serum Parathyroid hormone (PTH) (SMD = 0.73, 95%CI = 0.31 to 1.15, Z = 3.43, p = 0.0006) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.82, 95%CI = 0.33 to 1.30, Z = 3.29, p = 0.001) were elevated in NF1 patients, while serum calcium (SMD = -0.10, 95%CI = -0.74 to 0.53, Z = 0.32, p = 0.75) phosphorous (SMD = 0.33, 95%CI = -0.38 to 1.05, Z = 0.92, p = 0.36), alkaline phosphatase (ALP) (SMD = -0.36, 95%CI = -0.77 to 0.05, Z = 1.71, p = 0.09), osteocalcin (SMD = 1.81, 95%CI = -0.37 to -3.98, Z = 1.63, p = 0.10) and bone formation markers (SMD = 0.28, 95%CI = -0.37 to -0.94, Z = 0.85, p = 0.39) were not.
CONCLUSION
NF1 is associated with decreased BMD at the lumbar spine and femur. Taking into account that the serum levels of PTH, CTX were increased whereas the concentrations of vitamin D, calcium, phosphorous, ALP, osteocalcin and bone formation markers were not altered significantly in the NF1 patients compared with the healthy subjects, a vitamin D independent dysregulated bone cellular activity could be considered.
STUDY REGISTRATION
Registered on PROSPERO (CRD42023424751).
Topics: Adult; Child; Humans; Bone Density; Vitamin D; Neurofibromatosis 1; Calcium; Retrospective Studies; Cross-Sectional Studies; Osteocalcin; Parathyroid Hormone; Vitamins
PubMed: 38141750
DOI: 10.1016/j.bone.2023.116992