The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study

IntroductionElevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia.MethodsThis multi-center, prospective study enrolled patients aged 3–216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed.ResultsOverall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001).DiscussionQuestioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial RegistrationClinicaltrials.gov NCT04120168

Hodgkin Lenfoma; Beş Yaş Altındaki 102 Olgunun Retrospektif Analizi

Aim: To evaluate the clinical characteristics, treatment regimens, and outcome of the patients with Hodgkin lymphoma under five years old. Patients and methods: 102 patients diagnosed with Hodgkin lymphoma between 1972 and 2013 were retrospectively evaluated. All patients were treated with chemotherapy with or without radiotherapy. Chemotherapeutic regimens included COPP derivatives (cyclophosphamide or mustargen + vincristine + prednisolone + procarbazine), ABVD (Adriamycin + Bleomycin + Dacarbazine + Vinblastine), and alternated ABVD/COPP). Staging was done according to Ann Arbor classification system and histopathologic examination was done according to Rye system. Mean and median values were used for the demographic characteristics. Kaplan-Meier survival curves were used for survival analysis. The patient groups were compared in terms of survival duration using a log-rank test. Results: There were 81 males and 21 females with a median age of 4 years (2 to 4.9). 23 patients had B symptoms and 15 patients had bulky disease. Stage distributions were 45, 32, 16, and 9 patients in stage I, II, III, and IV, respectively. Histopathologic subtypes were mixed cellularity, nodular sclerosis, lymphocytic predominance, lymphocytic depletion, noduler lymphocyte predominant, unclassified in 63, 12, 11, 3, 2, 11 patients, respectively. Overall, and event-free survival rates were 89.7 and 74.8% with a median follow-up time of 13 years. OS rates were significantly different according to stage (p=0.008). Although there were no statistically significant difference, Bulky disease and B symptoms positivity were associated with poor prognosis. OS rates were 77 and 91.8 % in patients with and without bulky disaese, respectively (p=0.08). These rates were 77.8 % and 92.9% according to B symptom positivity (p=0.07).Amaç: Beş yaş altındaki Hodgkin lenfomalı olguların, klinik özellikleri, tedavi rejimleri ve sonuçlarının değerlendirilmesi. Hastalar ve Yöntem: 1972 ve 2013 yılları arasında Hodgkin lenfoma tanısı alan beş yaş altındaki102 olgu retrospektif olarak incelendi. Tüm olgular, COPP türevleri (Siklofosfamid veya nitrojen mustard+ onkovin + prednizolon + prokarbazin), ABVD (Adriamisin+ Bleomisin + Dakarbazin + Vinblastin), dönüşümlü ABVD/COPP kemoterapi rejimleri ve/veya radyoterapi ile tedavi edilmiştir. Evreleme Ann Arbor sınıflandırma sistemine ve histopatolojik inceleme Rye sistemine göre yapıldı. Demografik özellikler için ortanca değerler, yaşam analizi için Kaplan-Meier yaşam eğrileri kullanıldı. Log-rank testi ile de gruplar arasında yaşam süreleri karşılaştırıldı. Sonuçlar: Çalışmaya alınan 102 olguda erkek/kız oranı 3.8, ortanca yaş 4 (En küçük yaş iki, en büyük yaş 4.9). 23 olgunun B semptomu, 15 olgunun ise kitlesel (Bulky) lezyonu mevcuttu. Evrelere göre hastaların dağılımı ise sırasıyla I, II, III ve IV için 45, 32, 16, ve 9 hasta idi. Histopatolojik alt tiplerin dağılımı; karışık hücreli, noduler sklerozan, lenfositten zengin, lenfositten fakir ve noduler lenfosit baskın ve sınıflandırılamayan olmak üzere sırasıyla; 63, 12, 11, 3, 2, 11 olarak bulundu. Tüm grupta genel yaşam ve hastalıksız yaşam%89.7 ve %74.8. Genel yaşam hızları, evreye göre belirgin farklılık göstermekteydi (p=0.008). İstatistiksel olarak anlamlı farklılık saptanmamasına rağmen, kitlesel lezyon ve B semptom varlığının kötü prognozla ilişkili olabileceği düşünüldü. Genel yaşam; kitlesel lezyonu pozitif ve negatif olan hastalar için %77 ve %91.8 (p=0.08), B semptomları varlığında ise bu oranlar %77.8 ve %92.9 olarak belirlendi (p=0.07). Sonuç: Bu seri, beş yaş altı Hodgkin lenfomalı olgularla yapılan tek merkezli en büyük serilerden biridir. Erken evre hastalar, en iyi yaşam hızı oranlarına sahip olmakla birlikte; B semptomlarının varlığı ve kitlevi hastalık, kötü prognozla ilişkili bulunmuştur

Giant Omental Cyst (Lymphangioma) Mimicking Ascites And Tuberculosis

Omental and mesenteric cysts are both rare pathologies in children. Children who have omental cysts usually display symptoms of abdominal distension, with or without a palpable mass. The mass can simulate ascites on clinical observation, or tuberculosis on radiological images. The optimal treatment for this condition is complete resection. The presenting symptoms of abdominal distension and the simulation of septated ascites and abdominal tuberculosis are unusual. Reported cases in the literature usually display symptoms of abdominal distension, abdominal pain, painless mass or possible ascites. We describe the clinical presentation of a five-and-a-half-year-old boy who was treated for a diagnosis of abdominal tuberculosis and ascites at another hospital. After three years, he underwent abdominal surgery, and an omental cyst was found intraoperatively. The diagnosis was confirmed by pathological examination.PubMedWo

Does Nissen Fundoplication Improve Deglutition In Children?

A prospective study was performed to evaluate the effect of Nissen fundoplication (NF) on deglutition in children. Children who underwent NF between 2011-2015 were evaluated for demographic features, clinical findings, diagnostic methods for gastroesophageal reflux (GER) and indications for NF. Penetration aspiration scale (PAS), functional oral intake scale (FOIS) and esophageal functions were evaluated by videoflouroscopy (VFS). Preoperative and postoperative VFS findings were compared to evaluate the effect of NF on clinical findings and deglutition. Twenty-three children with a mean age of 5.08 +/- 3.7 years were included. Female to male ratio was 15:8. Recurrent respiratory infections (RTI) (n:14, 60.8%), swallowing dysfunction (n:13, 56.5%) and vomiting (n:10, 43.4%) were the most common symptoms. Preoperatively GER was diagnosed with barium swallowing study (BSS) contrast graphs (n:20, 87%) and with 24-hour esophageal pH monitorization (n:8, 34.8%). In 39.1% of patients, medical treatment for GER was used with a mean duration of 8 +/- 5.8 months. Indications for NF were swallowing dysfunction (n:18, 78%), GER complications (n:6, 26%), associated anatomical problems (n:4, 17.3%) and unresponsiveness to medical treatment (n:3, 13%). Postoperative barium swallowing study and 24-hour esophageal pH monitorization showed no GER after NF in 95% of patients. Number of RTI were significantly decreased after NF (preoperative vs postoperative infection rate 4.21 vs 1.6 respectively, p0.05). FOIS were significantly improved after NF (p<0.05). VFS findings showed that penetration and aspiration were significantly decreased after NF and children had less RTI. Although, esophageal motility evaluated by VFS did not changed after NF, functional oral intake significantly improved in children.WoSScopu

Biallelic CAV1 null variants induce Congenital Generalized Lipodystrophy with achalasia Short title: CAV1, generalized lipodystrophy and achalasia

International audienceObjective : CAV1 encodes caveolin-1, a major protein of plasma membrane microdomains called caveolae, involved in several signalling pathways. Caveolin-1 is also located at the adipocyte lipid droplet. Heterozygous pathogenic variants of CAV1 induce rare heterogeneous disorders including pulmonary arterial hypertension and neonatal progeroid syndrome. Only one patient was previously reported with a CAV1 homozygous pathogenic variant, associated with congenital generalized lipodystrophy (CGL3). We aimed to further delineate genetic transmission, clinical, metabolic and cellular characteristics of CGL3. Design/Methods: In a large consanguineous kindred referred for CGL, we performed next-generation sequencing, as well as clinical, imagery and metabolic investigations. We studied skin fibroblasts from the index case and the previously reported patient with CGL3. Results: Four patients, aged 8 months to 18 years, carried a new homozygous p.(His79Glnfs*3) CAV1 variant. They all displayed generalized lipodystrophy since infancy, insulin resistance, low HDL-cholesterol and/or high triglycerides, but no pulmonary hypertension. Two patients also presented at the age of 15 and 18 years with dysphagia due to achalasia, and one patient had retinitis pigmentosa. Heterozygous parents and relatives (n=9) were asymptomatic, without any metabolic abnormality. Patients’ fibroblasts showed a complete loss of caveolae and no protein expression of caveolin-1 and its caveolin-2 and cavin-1 partners. Patients’ fibroblasts also displayed insulin resistance, increased oxidative stress and premature senescence. Conclusions: The CAV1 null variant investigated herein leads to an autosomal recessive congenital lipodystrophy syndrome. Loss of caveolin-1 and/or caveolae induces specific manifestations including achalasia which requires specific management. Overlapping phenotypic traits between the different CAV1-related diseases require further studies

Clinical features of generalized lipodystrophy in Turkey: A cohort analysis

Aim: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. Methods: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. Results: The Kaplan–Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan–Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan–Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan–Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. Conclusions: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL