scholarly journals Clinical and Genetic Aspects of Juvenile Onset Pompe Disease

2021 ◽  
Author(s):  
Johanna Holzwarth ◽  
Nadja Minopoli ◽  
Charlotte Pfrimmer ◽  
Martin Smitka ◽  
Sabine Borrel ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Pompe Disease ◽  
Clinical Symptoms ◽  
Neuromuscular Disorders ◽  
Positive Family History ◽  
Clinical Signs ◽  
First Year ◽  
Juvenile Onset ◽  
Initial Symptoms ◽  
Genotypic Analysis

AbstractLittle is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1–17) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32–13T > G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype–phenotype correlation was poor.

scholarly journals CLINICAL MASKS OF ACUTE LEUKEMIA IN CHILDREN

2017 ◽  
Vol 4 (1) ◽  
pp. 9-13
Author(s):  
N.I. Makieieva ◽  
O.O. Afanasieva ◽  
V.A. Koval
Keyword(s):  
Acute Leukemia ◽  
General Practitioners ◽  
Clinical Symptoms ◽  
Correct Diagnosis ◽  
Clinical Signs ◽  
Case Histories ◽  
Initial Symptoms ◽  
Leukemia In Children

CLINICAL MASKS OF ACUTE LEUKEMIA IN CHILDRENMakieieva N.I., Afanasieva O.O., Koval V.A.For the study of initial clinical signs of acute leukemia in children 92 case histories have been analyzed. In most children the disease manifested with intoxication (94.6 ± 2,3%), lymphadenopathy (84,8±4,7%), hepatosplenomegaly (96,7±2,3%), anemic (82,6±4,9%), haemorrhagic (77,2±5,4%) syndromes. However, only in half of the cases the correct diagnosis was established in period less than 2-3 weeks since the first symptoms appeared. Consequently, it is necessary to pay attention of general practitioners to the variety of non-specific initial symptoms of acute leukemia in children.Keywords: acute leukemia, children, diagnostics, clinical symptoms КЛИНИЧЕСКИЕ МАСКИ ОСТРОГО ЛЕЙКОЗА У ДЕТЕЙМакеева Н.И., Афанасьева О.А., Коваль В.А.Для изучения начальных клинических признаков острого лейкоза у детей были проанализировано 92 истории болезни. В большинстве случаев заболевание начиналось с интоксикации (94,6 ± 2,3%), лимфаденопатии (84,8 ± 4,7%), гепатоспленомегалии (96,7±2,3%), анемического (82,6 ± 4,9) и геморрагического (77,2 ± 5,4) синдромов. Тем не менее, только в половине случаев правильный диагноз был установлен в период менее чем за 2-3 недели с момента появления первых симптомов. Следовательно, необходимо обратить внимание врачей общей практики на различные неспецифические начальные симптомы острого лейкоза у детей.Ключевые слова: острый лейкоз, дети, диагностика, клинические симптомы. КЛІНІЧНІ МАСКИ ГОСТРОЇ ЛЕЙКЕМІЇ У ДІТЕЙМакєєва Н.І., Афанасьєва О.О., Коваль В.А.Для вивчення початкових клінічних ознак гострої лейкемії у дітей було проаналізовано 92 історії хвороби. У більшості випадків захворювання починалося з інтоксикації (94,6 ± 2,3%), лімфаденопатії (84,8 ± 4,7%), гепатоспленомегалії (96,7 ± 2,3%), анемічного (82,6 ± 4, 9) та геморагічного (77,2 ± 5,4) синдромів. Проте, тільки в половині випадків правильний діагноз був встановлений в період менш ніж за 2-3 тижні з моменту появи перших симптомів. Отже, необхідно звернути увагу лікарів загальної практики на різні неспецифічні початкові симптоми гострої лейкемії у дітей. Ключові слова: гостра лейкемія, діти, діагностика, клінічні симптоми 

scholarly journals Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma

2015 ◽  
Vol 172 (2) ◽  
pp. 195-204 ◽  
Author(s):  
Frédérique Albarel ◽  
Caroline Gaudy ◽  
Frédéric Castinetti ◽  
Tiphaine Carré ◽  
Isabelle Morange ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Signs ◽  
Common Adverse Event ◽  
Common Side Effect ◽  
High Dose ◽  
The Third ◽  
Initial Symptoms ◽  
Long Term Follow Up

ObjectiveFew data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up.Design and patientsFifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille.MethodsSymptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded.ResultsOf 131 patients treated with ipilimumab or a placebo, 15 patients (10 mg/kg in 11/15) presented with hypophysitis (≥11.5%) at 9.5±5.9 weeks (mean±s.d.) after treatment start, occurring in 66% after the third infusion. The main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7–53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and ten gonadotroph functions. Pituitary imaging remained abnormal in 11 patients.ConclusionIpilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term.

Utility and Results from a Patient-Reported Online Survey in Myotonic Dystrophies Types 1 and 2

2020 ◽  
Vol 83 (5) ◽  
pp. 523-533
Author(s):  
Stephan Wenninger ◽  
Kristina Stahl ◽  
Federica Montagnese ◽  
Benedikt Schoser
Keyword(s):  
Muscle Weakness ◽  
Online Survey ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Neuromuscular Disorders ◽  
Gastrointestinal Symptoms ◽  
Online Surveys ◽  
Cardiac Symptoms ◽  
Significant Difference ◽  
Patient Reported

<b><i>Introduction:</i></b> Myotonic dystrophies (DMs) are the most frequent autosomal dominant neuromuscular disorders in adults. Our objective was to evaluate the utility of an online survey in a rare disease as well as to assess and compare the onset and the progression of clinical symptoms in patients with myotonic dystrophy types 1 (DM1) and 2 (DM2). <b><i>Methods:</i></b> We conducted a patient’s reported online survey assessing demographics, disease-related symptoms (age of onset, first symptom, time of diagnosis, current symptoms, inheritance, and family history) combined with capturing current symptoms by validated questionnaires. The questionnaire consisted of open, closed, single- and multiple-choice questions. Multiple answers were possible in some cases. Patients with genetically confirmed DM1 or DM2 who were registered in the German DM registry or the <i>Deutsche Gesellschaft für Muskelkranke e.V.</i> – Diagnostic Group for DMs were invited to participate in this online survey. We calculated descriptive and exploratory analysis, where applicable. <b><i>Results:</i></b> Out of 677 data sets from respondents, 394 were suitable for final analysis, containing completed questionnaires from 207 DM1 (56% female) and 187 DM2 patients (71% female). The median age of onset was 28 years for DM1 and 35 years for DM2. Muscular symptoms were most frequently reported as the first symptom. The onset of myotonia was earlier than the onset of muscle weakness in both DM1 and DM2. Forty-four percent of patients with DM1 and one-third of patients with DM2 indicated muscle weakness as the first symptom. Patients with DM1 were significantly younger when experiencing muscle weakness as first symptom. Fatigue was only mentioned by a small fraction of patients as a first symptom but increased significantly in the course of the disease. There was no statistically significant difference in the incidence of cataracts, cardiac symptoms, and gastrointestinal symptoms between DM1 and DM2. Falls were reported almost equally in both groups, and most of the patients reported 2–3 falls within the past year. <b><i>Discussion:</i></b> Overall, as our results are consistent with the results of clinical studies and online registries, it can be assumed that this type of systematic gathering of data from patients with rare diseases is useful and provides realistic and appropriate results. Due to the nature of online surveys and the absence of an assessor, some uncertainty remains. Furthermore, survey frauds cannot be completely excluded. An additional clinical assessment could confirm the given information and will improve the utility and validity of reported symptoms participants provide in online surveys. Therefore, we recommend a combination of data collecting by online surveys and clinical assessments.

scholarly journals Concentrations of canine prostate specific esterase, CPSE, at baseline are associated with the relative size of the prostate at three-year follow-up

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Bodil S. Holst ◽  
Sofia Carlin ◽  
Virginie Fouriez-Lablée ◽  
Sofia Hanås ◽  
Sofie Ödling ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Specific Antigen ◽  
Relative Size ◽  
Clinical Signs ◽  
Serum Concentrations ◽  
Prostatic Disease ◽  
Follow Up Study ◽  
Prostate Size ◽  
Prostate Growth

Abstract Background Enlargement of the prostate is associated with prostatic diseases in dogs, and an estimation of prostatic size is a central part in the diagnostic workup. Ultrasonography is often the method of choice, but biomarkers constitute an alternative. Canine prostate specific esterase (CPSE) shares many characteristics with human prostate specific antigen (PSA) and is related to prostate size. In men with clinical symptoms of prostatic disease, PSA concentrations are related to prostate growth. The aims of the present follow-up study were to evaluate if the concentration of CPSE is associated with future growth of the prostate, and if analysis of a panel of 16 steroids gives further information on prostatic growth. Owners of dogs included in a previous study were 3 years later contacted for a follow-up study that included an interview and a clinical examination. The prostate was examined by ultrasonography. Serum concentrations of CPSE were measured, as was a panel of steroids. Results Of the 79 dogs included at baseline, owners of 77 dogs (97%) were reached for an interview, and 22 were available for a follow-up examination. Six of the 79 dogs had clinical signs of prostatic disease at baseline, and eight of the remaining 73 dogs (11%) developed clinical signs between baseline and follow-up, information was lacking for two dogs. Development of clinical signs was significantly more common in dogs with a relative prostate size of ≥2.5 at baseline (n = 20) than in dogs with smaller prostates (n = 51). Serum concentrations of CPSE at baseline were not associated with the change in prostatic size between baseline and follow-up. Serum concentrations of CPSE at baseline and at follow-up were positively associated with the relative prostatic size (Srel) at follow-up. Concentrations of corticosterone (P = 0.024), and the class corticosteroids (P = 0.0035) were positively associated with the difference in Srel between baseline and follow-up. Conclusions The results support the use of CPSE for estimating present and future prostatic size in dogs ≥4 years, and the clinical usefulness of prostatic size for predicting development of clinical signs of prostatic disease in the dog. The association between corticosteroids and prostate growth warrants further investigation.

scholarly journals Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

2021 ◽  
Vol 22 (7) ◽  
pp. 3625
Author(s):  
Filomena Napolitano ◽  
Giorgia Bruno ◽  
Chiara Terracciano ◽  
Giuseppina Franzese ◽  
Nicole Piera Palomba ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Rare Variants ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Respiratory Muscles ◽  
Autosomal Recessive Disorder ◽  
Compound Heterozygous ◽  
Enzyme Replacement ◽  
Whole Exome ◽  
Clinical Pictures

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

370 Pure Primary Small Cell Carcinoma of the Prostate: A Rare Entity

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
C Desai ◽  
A Bhojwani ◽  
J Parkin
Keyword(s):  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Clinical Symptoms ◽  
Positive Family History ◽  
Malignant Neoplasm ◽  
Small Cell ◽  
Whole Body ◽  
Carcinoma Of The Prostate ◽  
Patient Reported ◽  
Prostate Cancers

Abstract Introduction We report a case of small cell carcinoma of the prostate (SCCP) which is a rare, high-grade malignant neoplasm accounting for 1% of all prostate cancers (CPa). Case Presentation A 56-year-old male patient initially presented to primary care with a six-month history of frequency, nocturia and pain in the perineal region when seated. A positive family-history for CPa was noted, serum PSA was 11.58, and a rectal examination found a large, irregular mass. He was treated with antibiotics for possible prostatitis and referred to the colorectal team. MRI rectum confirmed a mass between the prostate and rectum, which was found to be pure SCCP on biopsy. Whole-body scanning found multiple lung and pelvic metastases. The patient was commenced on six cycles of Etoposide and Carboplatin therapy. The patient reported that his pelvic discomfort has improved following the first cycle. Conclusions SCCP metastasizes early and therefore the clinical presentation is often in an advanced stage. It is noted that there is limited value of serum PSA for SCCP diagnosis. Instead, pathological examinations and MRI rectum are vital. In terms of treatment, chemotherapy provides relief of the clinical symptoms and its use is in in accordance with the 2016 National Comprehensive Cancer Network guidelines.

The outcome of seven patients with hereditary tyrosinemia type 1

2016 ◽  
Vol 29 (10) ◽  
Author(s):  
Songul Gokay ◽  
Pembe Soylu Ustkoyuncu ◽  
Fatih Kardas ◽  
Mustafa Kendirci
Keyword(s):  
Clinical Symptoms ◽  
Age At Onset ◽  
Nodule Formation ◽  
First Year ◽  
Tyrosine Metabolism ◽  
Tyrosinemia Type 1 ◽  
Hereditary Tyrosinemia ◽  
Biochemical Imaging

AbstractBackground:Hereditary tyrosinemia type 1 (HT1) is a rare, inborn error of tyrosine metabolism. It is a fatal disorder without treatment. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival. The aim of the present study is to describe the clinical, biochemical, imaging and follow-up of seven patients with HT1 and to define the consequences of the late and interrupted treatment.Methods:A retrospective study was carried out with seven HT1 patients.Results:The median age at onset of clinical symptoms was 11.2 months (range, 3–28 months) and the median age at diagnosis was 22 months (range, 6–58 months). Liver enzymes and coagulation parameters were back to normal in all symptomatic patients in about 2 weeks. Alfa-fetoprotein (AFP) levels were normalized within the first year of therapy. Hypoechoic nodule formation was detected in two of the seven patients despite drug treatment without an increase of AFP and any dysplastic changes in the biopsies. One patient died due to metastatic HCC because of the late diagnosis and the poor compliance of the follow-up.Conclusions:This study showed once again that adherence to the treatment and a follow-up schedule of the patients are very important. Also it should not be forgotten that nodule formation can occur despite nitisinone treatment without an increase of AFP. Despite nitisinone treatment, HT1 patients still carry the risk of HCC. HCC must be detected before metastasis to other organs otherwise, patients may lose the chance for liver transplantation.

RENAL HISTOLOGY DURING TREATMENT WITH OXAZOLIDINE-DIONES (TRIMETHADIONE, ETHADIONE, AND PARAMETHADIONE)

PEDIATRICS ◽  
1962 ◽  
Vol 30 (4) ◽  
pp. 601-607
Author(s):  
A. Bergstrand ◽  
C. G. Bergstrand ◽  
N. Engström ◽  
K. M. Herrlin
Keyword(s):  
Electron Microscopy ◽  
Nephrotic Syndrome ◽  
Renal Disease ◽  
Renal Biopsy ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Present Knowledge ◽  
Short Report ◽  
Renal Histology ◽  
Renal Changes

Seven patients with petit mal seizures treated with trimethadione, ethadione, or paramethadione for long periods were subjected to renal biopsy at the age of 14½ 16½ years. None of the patients had clinical signs of renal disease at the time of the biopsy, but three of them had previously shown transient hematuria or proteinuria. The renal histology was studied by conventional methods and by electron microscopy, the latter method only including the glomeruli. The changes found must with the present knowledge be regarded as physiological. A short report is given of a patient with phenylketonuria and epilepsy who developed a nephrotic syndrome during treatment with tridione. No definite pathologic renal changes were demonstrated at the when the clinical symptoms had disappeared.

MO765CENTRAL VEIN STENOSES IN HD PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Aleksei Zulkarnaev ◽  
Andrey Vatazin ◽  
Vadim Stepanov ◽  
Ekaterina Parshina ◽  
Mariya Novoseltseva
Keyword(s):  
Risk Factor ◽  
Vascular Access ◽  
Dwell Time ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Cox Proportional Hazards ◽  
Important Risk Factor ◽  
Central Vein ◽  
Increased Risk ◽  
The Mean

Abstract Background and Aims The prevalence of central vein stenosis (CVS) in patients on hemodialysis (HD) is difficult to be assessed directly. This is mainly caused by the variety of clinical signs and the high frequency of asymptomatic CVS. Aim: to assess the frequency of occurrence of various CVS forms in HD patients. Method The retrospective observational study is based on the results of treatment of 1865 HD patients who underwent diagnostic and therapeutic procedures on vascular access in our center. In case of vascular access dysfunction, patients were examined according to a local protocol: ultrasound of the peripheral (to exclude lesion of peripheral AVF segments) and central veins (over the available length), followed with CT-angiography or percutaneous angiography, if necessary. Results AVF/AVG dysfunction was observed in 29.4% of patients (549 of 1865). 211 patients were diagnosed with CVS. The prevalence of CVS was 11.3% (211 of 1865) among all HD patients and 38.4% (211 of 549) in patients with AVF dysfunction. Among patients with CVS, 37% (78 of 211) had vein lesions without clinical symptoms or with minimal manifestations (a tendency to decrease KT/V). The prevalence of asymptomatic CVS was 4.2% (78 of 1865) in the general population of HD patients and 14.2% (78 of 549) in patients with AVF dysfunction. In case of asymptomatic CVS it was detected by an ultrasound examination during CVC implantation (N=38), during unsuccessful attempts to implant CVC (N=29), in the case of recurrent AVF thrombosis without underlying peripheral segments lesion (N=9) or during echocardiography (N=2). The prevalence of asymptomatic CVS among patients without AVF dysfunction was 5.9% (78 of 1316). True prevalence of subclinical CVS among HD patients without obvious signs of AVF dysfunction may vary widely. A total of 48.8% (103 of 211) of all CVS cases were treated. At the same time, in 10.7% (11 of 103) of cases, patients did not present symptoms of CVS, and surgery was performed due to recurrent AVF thrombosis without damage of the peripheral parts of AVF. Patients with clinically manifest CVS who received endovascular interventions had a significantly higher risk of AVF loss compared to patients with asymptomatic CVS: HR=2.566 [95% CI 1.706; 3.86], log rank p&lt;0.0001. However, patients with an asymptomatic CVS had a higher risk of AVF function loss compared to the general HD population (HR=2,051 [95% CI 1,243; 3,384], log rank p= 0.0004) – fig. 1. The use of CVC is a known risk factor of CVS development. We analyzed the relationship of CVS risk with multiply CVC placements and catheter dwell time using the Cox proportional hazards regression model (fig. 2). In the univariate model, a greater No of CVCs as well as longer time in place increased the risk of CVS. In the multivariate model (χ2=105.516, df=2, p&lt;0.0001), catheter dwell time was no longer associated with an increased risk of CVC, while the mean number of inserted catheters remained an important risk factor. Conclusion The prevalence of both symptomatic and asymptomatic forms of CVS in HD patients is high. Patients with vascular access dysfunction should be carefully examined to identify the asymptomatic CVS. The mean No of catheterizations is a more important risk factor of CVS than longer catheter dwell time.

Sign in / Sign up

Export Citation Format

Share Document