Primary congenital glaucoma in Denmark, 1977-2016.

BackgroundRare diseases are often un- or misdiagnosed for extended periods, resulting in a long diagnostic delay that may significantly add to the burden of the disease. An early diagnosis is particularly essential if a disease-modifying treatment is available. The purpose of this study was to assess the extent of the diagnostic delay in the two ultra-rare diseases, i.e., mucopolysaccharidosis I (MPS I) and III (MPS III), both of which are lysosomal storage disorders with different phenotypic severities (MPS 1 is characterized by the severe Hurler and the more attenuated non-Hurler phenotypes, MPS III is characterized by the severe rapidly progressing (RP) phenotype and more attenuated slowly progressing (SP) phenotype). We investigated whether the diagnostic delay changed over the previous decades.ResultsThe diagnostic delay, which is defined as the time between the first visit to a medical doctor for disease-related symptoms and the final diagnosis, was assessed using telephone interviews with patients diagnosed between 1988 and 2017 and/or their parents or legal guardian(s). In addition, the medical charts were reviewed. For MPS I (n = 29), the median diagnostic delay was 8 months (range 1-24 months) for Hurler patients and 28 months (range 2-147 months) for non-Hurler patients. For MPS III (n = 46), the median diagnostic delay was 33 months (range 1-365 months). No difference was observed between the RP and SP phenotypic groups. Comparing the diagnostic delay over time using 5-year time intervals, no reduction in the diagnostic delay was observed for MPS I or MPS III.ConclusionsIn the Netherlands, the time to diagnosis for patients with MPS I and MPS III has not changed between 1988 and 2017, and an extensive delay still exists between the first visit to a medical doctor for disease-related symptoms and the final diagnosis. The numerous campaigns launched to increase awareness, leading to earlier diagnosis of these rare disorders, particularly of MPS I, have failed to achieve their goal. Robust selected screening protocols embedded in national guidelines and newborn screening for disorders that meet the criteria for population screening may be the only effective approaches for reducing the diagnostic delay.

The purpose of this study was to report the outcomes of Silicone Ahmed Glaucoma Valve (AGV) implantation in the management of refractory pediatric glaucoma. Between 2007 and 2015, 76 eyes of 64 children aged 16 years or younger underwent AGV implantation. We included 65 eyes of 53 children with follow up ≥6 months; 24 eyes had primary congenital glaucoma (PCG) and 41 eyes had secondary pediatric glaucoma (SPG). Success was defined as IOP>5 and ≤21 mm Hg with or without topical antiglaucoma medications; considered failure, when repeat glaucoma surgery was need or loss of light perception. Primary outcome measure was success of AGV in refractory pediatric glaucomas and secondary outcome measure was comparison of outcomes in PCG and SPG. The median age at AGV implantation was 3 years (interquartile range, 2, 12), and median follow up was 27 months (15, 39). The overall cumulative success probability was 88% [95% confidence interval (CI), 76%-94%] at 1 year and was maintained up to 4 years. The success probability in PCG was 91% (80.8%-100%), and SPG was 83% (72%-96%) at 1 year and 4 years (P=0.49). Among the preoperative factors, number of previous intraocular surgeries (hazard ratio of 2.24; 95% CI, 1.14-4.37, was significantly associated with failure; P=0.01). Tube-related complications (16%) were similar in both the groups. One eye in each group had sight-threatening complication. AGV implantation had good success rate in refractory pediatric glaucoma. The success rates were similar in PCG and SPG as were the complications. Number of prior intraocular surgeries was a risk factor for failure.

Giant Cell Tumor of Bone is an intermediate, locally aggressive tumor that is often diagnosed at an advanced stage due to diagnostic delays. Hypothetically, diagnostic delays may result in advanced disease, necessitating more invasive surgery and causing significant lifelong burden. This systematic review explores the available literature on diagnostic and treatment delays in Giant Cell Tumor of Bone. A systematic review was conducted using the Medline, Embase, and Cochrane databases on February 9, 2023. A total of 15 studies representing 34 cases (32 cases analyzed) were included after thorough review and critical appraisal. Fifteen articles representing 32 cases were included. The median age of the included cases was 29 years (IQR 24-41). Tumor locations included the foot (22%), spine (19%), distal ulna (16%), and other sites (43%). Campanacci grades 2 and 3 (used to assess tumor severity) were reported in 16% and 81% of cases, respectively. Primary GCTB accounted for 88% of cases, while 12% involved local recurrence. The median diagnostic delay was 5.5 months (IQR 3.0-13.5). Patient-related delays (13 cases) had a median of 6 months (IQR 3-35), referral delays (19 cases) had a median of 4 months (IQR 3-12), and diagnostic delays (4 cases) had a median of 2.5 months (IQR 1-4). Diagnostic delays in Giant Cell Tumor of Bone were identified, and were often associated with advanced disease. Further research involving a larger number of cases is essential to assess the impact of these delays on clinical outcomes and disease progression.

ObjectivesTo study the diagnostic delay for pituitary stalk interruption syndrome (PSIS) with growth hormone deficiency (GHD) and the sensitivity of the auxological criteria of the Growth Hormone Research Society (GHRS) consensus guidelines.MethodsA single-center retrospective case-cohort study covering records from January 2000 through December 2007 evaluated the performance of each GHRS auxological criterion for patients with GHD and PSIS. Diagnostic delay was calculated as the difference between the age at which the earliest GHRS criterion could have been observed and the age at diagnosis of PSIS with GHD. A diagnostic delay exceeding one year was defined as late diagnosis.ResultsThe study included 21 patients, 16 (76%) of whom had isolated GHD and 5 (24%) multiple pituitary hormone deficiencies. The median age at diagnosis was 3.6 years (interquartile range, IQR, 2.6–5.5). The median diagnostic delay was 2.3 years (range 0–12.6; IQR 1.5–3.6), with late diagnosis for 17 patients (81%). Height more than 1.5 SDS below target height was the most effective criterion: 90% of the patients met the criterion before diagnosis at a median age of 1 year, and it was the first criterion to be fulfilled for 84%.ConclusionIn our cohort, the delay for diagnosis of PSIS with GHD was long and could have been reduced by using the GHRS criteria, in particular, height more than 1.5 SDS below the target height. The specificity of such a strategy needs to be tested in healthy populations.

Evaluation of long-term functional and structural outcomes in patients with primary congenital glaucoma (PCG) based on visual acuity (VA), visual field (VF) using standard automated perimetry, and peripapillary retinal nerve fibre layer thickness (pRNFL). We retrospectively reviewed medical records of all patients diagnosed with PCG in Denmark from 1977 to 2016. Severe vision loss was defined as VA <6/60 and/or VF >20 decibels (dB). Prognostic factors were evaluated in a correlation matrix. The median age of the 94 patients (153 PCG eyes) was 12 years (IQR 9-16). In PCG eyes 62% had VA ≥6/18 but 22% had <6/60. VA in the better seeing eye was ≥6/18 in 90% and <6/60 in 5%. VF was measured in 59 PCG eyes and the median mean defect was 5.1 dB (IQR 2.1-9.6) with 52% better than 6 dB and 9% worse than 20 dB. Generalized pRNFL was reduced below the age-expected 1st percentile in 29% of the 58 PCG eyes where pRNFL was measured. Poor VA, poor VF and reduced pRNFL were all correlated (p = 0.0001). More surgeries (p < 0.0001) and longer diagnostic delay (p = 0.004) were associated with poorer vision and to a lesser degree with poor VF pRNFL. In Denmark, most patients with bilateral PCG retain VA ≥6/18 in the better seeing eye. Poor VA was associated with poor VF. Longer diagnostic delay and more surgeries were associated with a poorer prognosis.

To determine the spectrum of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma, and to correlate the presence of alterations in the CYP1B1 gene sequence with clinical aspects of the disease. Thirty nonrelated patients with primary congenital glaucoma were studied. Molecular analysis consisted of the codifying region sequencing (exons 2 and 3) and intron/exon boundaries. CYP1B1 gene mutations were present in 9 (30%) of the 30 patients. The structural changes in the CYP1B1 gene previously described in the literature and observed in our study were Q19X, P437L, A443G, g.4340delG, g.7901_79013delGAGTGCAGGCAGA, g.8182delG, and g.8214_8215delG. Three new mutations were observed: 4635delT, 4523delC, and L378Q, in addition to 3793T→C, R48G, A119S, L432V, D449D, and N453S polymorphisms. Patients carrying CYP1B1 gene mutations needed more surgical procedures to control intraocular pressure, either when both eyes were evaluated (P=0.003) or when the worst eye of the patient was analyzed (P=0.011). In relation to the number of affected eyes, all patients with mutations (n=9/9) developed bilateral glaucoma, whereas 11/21 patients without mutations in the CYP1B1 gene had bilateral glaucoma (P=0.013). In this group of primary congenital glaucoma patients, a 30% mutation frequency in the CYP1B1 gene was observed. The presence of mutations was associated with a more severe form of the disease, requiring more surgeries for intraocular pressure control and with a higher rate of bilateral cases.

Common variable immunodeficiency (CVID) is the most clinically significant primary antibody immunodeficiency recognized in adulthood. Previously published data have shown an average diagnostic delay of 10 years for Polish adult patients with CVID. In the current study, we aimed to analyze the current diagnostic delay of adult patients with CVID in Poland. To this end, we identified patients from four immunological centers specialized in the care of adult patients with primary immunodeficiencies (PID). Demographic and clinical data of patients were collected using an internet database. We identified 103 adult patients (F:M 44.7%:55.3%) in Poland with CVID. The median age at onset of symptoms was 24 (0–66), 33 (4–70) at diagnosis, and 37 (18–73) years at the time of analysis. The median diagnostic delay for the entire study population was 6 (0–57) years. However, this delay was higher in patients with symptom onset before the year 2000 than after the year 1999 [15 (0–57) vs. 3 (0–19) years; p < 0.001]. Comparing patients (median ≤ 6 years, N = 53) with short diagnostic delay (SDD) and those (median > 6 years, N = 50) with long diagnostic delay (LDD), the LDD group had a statistically significant higher incidence of infections of the lower respiratory tract before diagnosis (90.0 vs. 71.70%). During the entire observation period, cytopenias (44.00 vs. 22.64%), granulomatous lesions (28.00 vs. 11.32%), and solid tumors (14.00 vs. 1.89%) were significantly more frequent in the LDD group. In conclusion, we found a significant reduction in the median diagnostic delay in Polish CVID patients with disease onset in the last two decades.

BACKGROUNDStudies investigating diagnostic delays and their effects on patients with alcoholic cirrhosis.AIMTo investigate the current status and associated factors influencing diagnostic delays in 401 patients with alcoholic cirrhosis.METHODSA cross-sectional analysis was conducted at a tertiary hospital in China from June 2020 to December 2023. Data were collected through telephone follow-ups and questionnaires. The Wilcoxon and Kruskal-Wallis H tests were used to compare diagnostic delays across various characteristics. Multivariate linear regression was employed to identify factors associated with diagnostic delays.RESULTSThe median diagnostic delay was 5 months, with an interquartile range of 2-11 months. The proportions of patients with alcoholic cirrhosis who initially visited tertiary, secondary, and primary hospitals were 38.9%, 37.91%, and 23.19%, respectively. Furthermore, the rates of patients undergoing liver computed tomography (CT) during their first visit at tertiary, secondary, and primary hospitals were 92.95%, 13.82%, and 1.08%, respectively (P < 0.001). Significant differences were observed in diagnostic delay-related characteristics, including residence, resident type, initial diagnosis, medical insurance, liver CT, and liver ultrasound during the first visit, age, years of education, family size, marital status, annual family income, years of drinking, daily alcohol consumption, and type of alcohol consumed (P < 0.01). Furthermore, diagnostic delays were variably associated with daily alcohol consumption and other characteristics (i.e. residence, years of drinking, medical insurance, years of education, annual family income, liver CT and ultrasound during the first visit). Significant predictors of diagnostic delay identified on multivariate linear regression analysis included years of education, daily alcohol consumption, annual family income and blood ammonia levels (P < 0.01). Patients with alcoholic cirrhosis experience varying degrees of diagnostic delays, necessitating interventions targeting potential contributing factors.CONCLUSIONOur study indicates that patients with alcoholic cirrhosis may experience varying degrees of diagnostic delay. Interventions targeting potential factors contributing to diagnostic delay are necessary.

Background and Aims: A delay in the diagnosis of inflammatory bowel disease (IBD) is a risk of developing complications and surgery. This study was done to evaluate the factors and impact of diagnostic delay on IBD patients in Bangladesh. Methods: This cross-sectional study was carried out in the Department of Gastroenterology of a tertiary care center in Bangladesh. Diagnostic delay was defined as the period from symptom onset to diagnosis of IBD. Results: Of the total 112 IBD patients 50 (44.6%) had Crohn’s disease CD and 62 (55.4%) had ulcerative colitis (UC). Males (67.9%) were predominant in the study. The median diagnostic delay was longer for patients with CD compared with patients with UC (median 24 versus 12 months; P-value 0.025). Rectal bleeding as presenting feature and male gender were negatively and positively associated with the longer diagnostic delay of IBD respectively (P-value &lt;0.05). Of the patients with CD 14 (28%) had a history of IBD-related surgery and 7 (14%) had a history of perianal fistula. The presence of intestinal strictures, surgery, and perianal fistula at the time of diagnosis was significantly associated with long diagnostic delay for CD. Conclusion: Absence of rectal bleeding as presenting symptoms and also the male gender were the significant factors related to the longer diagnostic delay of IBD in our study. Long diagnostic delay is associated with an increased rate of complications in IBD, especially in CD.

BackgroundCaroli syndrome (CS) is a rare congenital disorder without pathognomonic clinical symptoms or laboratory findings; therefore, the diagnosis is often delayed. The objective of this study was to investigate the diagnostic delay and associated risk factors in CS patients.MethodsThis was a retrospective analysis of 16 CS patients admitted to a single tertiary medical center on mainland China. The diagnostic timelines of CS patients were reviewed to demonstrate the initial findings of CS at diagnosis, the risk factors associated with diagnostic delay, and potential clues leading to early diagnosis.ResultsThe median diagnostic delay was 1.75 years (range: 1 month to 29 years, interquartile range: 6.2 years) in 16 enrolled CS patients. Sex, age, and initial symptoms were not associated with diagnostic delay. 87.5% of CS patients were diagnosed by imaging, and the accuracies of ultrasonography, computed tomography (CT), and magnetic resonance cholangiopancreatography were 25, 69.2, and 83.3%, respectively. The median diagnostic delays for patients with or without CT performed at the first hospital visited according to physician and radiologist suspicion of the diagnosis were 7.4 months and 6 years, respectively (p = 0.021). Hepatic cysts with splenomegaly were detected by ultrasound in over half of CS patients.ConclusionsThe majority of CS patients were not diagnosed until complications of portal hypertension had already developed. Recognition and early suspicion of the disease were important factors influencing diagnostic delay of CS. Hepatic cysts plus splenomegaly detected by US might raise the clinical suspicion to include CS in the differential diagnosis.

Delayed diagnosis seems to be common in inflammatory bowel diseases (IBD). The study was carried out to investigate the diagnostic delay and associated risk factors in Austrian IBD patients. In amulticenter cross-sectional study adult patients with IBD attending 18Austrian outpatient clinics completed amulti-item questionnaire that recorded medical and socioeconomic characteristics. The study outcome was diagnostic delay defined as the period from symptom onset to diagnosis of IBD. Atotal of 1286 patients (Crohn's disease 830, ulcerative colitis 435, inflammatory bowel disease unclassified 21; females 651) with amedian age of 40years (interquartile range 31-52years) and amedian disease duration of 10years (4-18years) were analyzed. The median diagnostic delay was 6months (2-23months) in Crohn's disease and 3months (1-10months) in ulcerative colitis (p < 0.001). In the multivariable regression analysis Crohn's disease, greater age at diagnosis and ahigh educational level (compared to middle degree level) were independently associated with longer diagnostic delay. The diagnostic delay was longer in Crohn's disease than in ulcerative colitis patients and was associated with greater age at diagnosis and ahigher educational level.

The magnitude of the diagnostic delay of symptomatic uncomplicated diverticular disease (SUDD) is unknown; we aimed to evaluate SUDD diagnostic delay and its risk factors. SUDD patients diagnosed at a tertiary referral centre were retrospectively enrolled (2010–2022). Demographic and clinical data were retrieved. Overall, patient-, and physician-dependant diagnostic delays were assessed. Univariate and multivariate analyses were fitted to identify risk factors for diagnostic delay. Overall, 70 SUDD patients (median age 65 years, IQR 52–74; F:M ratio = 1.6:1) were assessed. The median overall diagnostic delay was 7 months (IQR 2–24), patient-dependant delay was 3 months (IQR 0–15), and physician-dependant delay was 1 month (IQR 0–6). Further, 25% of patients were misdiagnosed with irritable bowel syndrome (IBS). At multivariate analysis, previous misdiagnosis was a significant risk factor for overall and physician-dependant diagnostic delay (OR 9.99, p = 0.01, and OR 6.46, p = 0.02, respectively). Also, a high educational level (> 13 years) was associated with a greater overall diagnostic delay (OR 8.74 p = 0.02), while previous abdominal surgery was significantly associated to reduced physician-dependant diagnostic delay (OR 0.19 p = 0.04). To conclude, SUDD may be diagnosed late, IBS being the most frequent misdiagnosis. Timely diagnosis is crucial to tackle the burden of SUDD on patients and healthcare.

T.P.16: Clinical and molecular characteristics of 33 patients with Late Onset Pompe Disease (LOPD): Unusual phenotypes, novel mutations and therapeutic responses

Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms. The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD. Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up. Forty-five patients were identified (median age: 49, range: 40-64) and placed in three groups according to their clinical presentation: neurological (n=20, median diagnostic delay: 20months), hepatic (n=13, diagnostic delay: 12months), and family screening (n=12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser-Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis. In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The DRC faces the paradox of high mortality and low incidence of breast cancer due to late consultations and delayed treatment; however, it lacks studies detailing the different delays of breast cancer management. We initiated this study to assess these delays and identify the associated factors. Methods: This was a cross-sectional study conducted on 201 records of women followed for breast cancer at the University Clinics of Kinshasa (UCK) from January 2020 to December 2024. Population characteristics and delays were described using descriptive statistics, logistic regression was used to identify factors associated with delays. Results: The mean age was 48±12 years. 90.8% of patients were diagnosed at advanced stages, 67% received chemotherapy as first treatment. The median patient delay was 365 days, the median diagnostic delay was 26 days, the median treatment delay was 39 days, the median health system delay was 67 days, the median total delay was 398 days. Single women had a higher risk of consultation delay (aOR=2.48; p=0.02), diagnostic delay (aOR=1.79 p=0.01) and treatment delay (aOR=3.67; p=0.04). Women who followed alternative pathways had a higher risk of delay in consultation (aOR=9; p=0.01), diagnosis (aOR=3.27; p=0.02), and treatment (aOR=3.27; p=0.01). Consulting for symptoms other than breast lump was associated with a higher risk of treatment delay (aOR=3.44; p=0.02). Conclusions: Efforts must be made to address the causes of delayed consultations and to improve the patient care pathway.