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.

Evaluation of non-infectious complications in children receiving parenteral nutrition.

BACKGROUND: Parenteral nutrition may lead to inevitable complications. AIMS: To determine the indications, metabolic and mechanical complications of parenteral nutrition in children. METHODS: One hundred fifty-eight children (91 males; 57.8%) who received 179 episodes of individualized parenteral nutrition for ≥ 5 days within 2 years were analyzed. Indications and duration of parenteral nutrition, effect on growth, and metabolic and central venous catheter-related non-infectious complications were evaluated. RESULTS: Parenteral nutrition was administered in 179 different episodes (109 males; 60.9%), and the median age during these episodes was 64.0 (14.0-129.0) months. The most common indications were hematological malignancies, gastrointestinal surgery, and hematopoietic stem cell transplantation. Most of the electrolyte imbalances occurred in the first 3 days. Hypophosphatemia (44.7%), hypomagnesemia (43.0%), hypokalemia (43.0%), hyponatremia (40.8%), and hypertriglyceridemia (38.2%) were the most common metabolic complications. Liver transaminases elevated in 32/145 (22.1%) episodes and bilirubin in 30/149 (21.0%). Ursodeoxycholic acid treatment was added to 25 patients with hypertransaminasemia and/or hyperbilirubinemia. Transaminase levels improved in 16 (64%) and bilirubin levels in 15 (60%) patients receiving ursodeoxycholic acid. Catheter thrombosis was seen in 4.5% of the episodes. The targeted energy could be given more efficiently via central catheters rather than peripheral venous accesses. Patients' bodyweights increased in 39.1% of the episodes. CONCLUSIONS: Close monitoring of electrolyte levels, especially in the first 3 days, is crucial to prevent complications of parenteral nutrition. When individualized PN preparations are used for metabolically unstable patients, it can be easier to maintain the blood glucose, lipids, and electrolyte levels within the normal range.

Nutritional status of children with primary immunodeficiency: A single center experience.

BACKGROUND: Nutritional status in primary immunodeficiencies (PID) is a major factor influencing immune defense. We aimed to evaluate the nutritional status of patients with PID. METHODS: Demographic findings and anthropometric measurements of 104 patients were recorded for this cross-sectional study. RESULTS: Combined immunodeficiencies (n = 49), predominantly antibody deficiencies (n = 28) and phagocytic system disorders (n = 17), were the major disease groups. In total, 44 (42.3%) patients had at least one anthropometric measurement below -2 standard deviations. Chronic, acute, and mixed-type malnutrition were detected in 18.3%, 16.3%, and 7.7% of the patients, respectively. No significant difference was detected among groups regarding anthropometric measurements however higher malnutrition rates were observed in 'combined immune deficiency less profound than severe combined immuno deficiency' (52%), chronic granulomatous disease (66.6%), and X-linked agammaglobulinemia (50%) patients. Severe malnutrition was present in 22 (21.2%) of the patients, although it was not significant. It was more common in the phagocytic system disorder group. All patients in the severe combined immunodeficiency group had undergone hematopoietic stem cell transplantation and 50% of them had malnutrition. There was also no significant difference regarding age, sex, anthropometric indexes (Weight for age, lenght/height for age body mass index Z-scores), malnutrition types, and prevalence of malnutrition among three major disease groups. Only the hospitalization history inversely related to body mass index and weight for age Z-scores (P < 0.0001). In patients with malnutrition, daily caloric intake was at least 20% or more below the requirement. CONCLUSIONS: Regardless of the type of immunodeficiency, nutritional status was poor in PID and hospitalization is the most important determinant of nutritional status. Even after hematopoietic stem cell transplantation, nutritional support should be continued.

Biallelic CAV1 null variants induce congenital generalized lipodystrophy with achalasia.

OBJECTIVE: CAV1 encodes caveolin-1, a major protein of plasma membrane microdomains called caveolae, involved in several signaling 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.

Does Nissen fundoplication improve deglutition in children?

Soyer T, Yalçin S, Demir N, Karhan AN, Saltik-Temizel IN, Demir H, Tanyel FC. Does Nissen fundoplication improve deglutition in children? Turk J Pediatr 2017; 59: 28-34. 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, p < 0.05). VFS findings showed that PAS was significantly decreased after NF during both liquid and semi-liquid swallowing (p < 0.05). After NF, upper esophageal opening (UEO) was decreased when compared to preoperative VFS findings (p < 0.05 Esophageal cleaning, esophageal motility, esophageal backflow and lower esophageal sphincter narrowing did not alter after NF (p > 0.05). 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.

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.