A Rare Cause of Recurrent Acute Pancreatitis in a Child: Isovaleric Acidemia with Novel Mutation

Elif Sag,Alper Han Cebi,Gulay Kaya,Gulay Karaguzel,Murat Cakir 대한소아소화기영양학회 2017 Pediatric gastroenterology, hepatology & nutrition Vol.20 No.1

Recurrent acute pancreatic attacks is a rare clinical condition (2-5% of all acute pancreatis) in children and is mainly idiopathic in most cases. Sometimes it may be associated with congenital anomalies, metabolic diseases or heredi-tary conditions. Isovaleric acidemia (IVA) is a rare autosomal recessive amino acid metabolism disorder associated with isovaleryl coenzyme A dehydrogenase deficiency presenting the clinical findings such metabolic acidosis with increased anion gap, hyperammonemia, ketonemia, hypoglycemia, “the odor of sweaty feet,” abdominal pain, vomit-ing, feeding intolerance, shock and coma. Recurrent acute pancreatitis associated with IVA have been rarely reported. Herein; we report a child who admitted with recurrent acute pancreatic attacks and had the final diagnosis of IVA. Mutation analysis revealed a novel homozygous mutation of (p.E117K [c.349G>A]) in the IVA gene. Organic acidemias must kept in mind in the differential diagnosis of recurrent acute pancreatic attacks in children.

Acquired noncaustic esophageal strictures in children

Sag, Elif,Bahadir, Aysenur,Imamoglu, Mustafa,Sag, Sefa,Reis, Gokce Pinar,Erduran, Erol,Cakir, Murat The Korean Pediatric Society 2020 Clinical and Experimental Pediatrics (CEP) Vol.63 No.11

Background: Esophageal stricture (ES) is an uncommon clinic entity in pediatrics that may be congenital or acquired in childhood. Acquired noncaustic ES is very rare, and clinical features of affected patients are unknown. Purpose: We aimed to evaluate the clinical findings, and outcomes of patients with acquired noncaustic ES to aid physicians in the early referral of patients to gastroenterologists. Methods: The medical data of patients with acquired noncaustic ES who were followed in our gastroenterology clinic between January 2009 and December 2019 were reviewed. Results: Acquired noncaustic ES was found in 12 of the 4,950 patients (0.24%) who underwent endoscopy during the study period. The main symptoms were dysphagia (58.3%), vomiting (33.3%), and chronic anemia (8.3%). Chronic malnutrition and underweight were found in 66.6% of the patients. The most common etiological factors were radiotherapy, peptic reflux, and achalasia (16.6%, each), while chemotherapy, squamous-cell carcinoma (SC) of the esophagus, eosinophilic esophagitis (EoE), esophageal web, epidermolysis bullosa, and esophageal diverticulum (8.2%, each) were the other etiological factors. Patients with EoE underwent endoscopic bougie dilation in addition to steroid use and elimination diet. Patients with epidermolysis bullosa and esophageal web underwent bougie dilation. Patients with peptic reflux-related ES were initially put on antireflux therapy, but during follow-up, one patient required esophageal replacement with colonic interposition. Patients with radiotherapy-related ES recovered with medical therapy. The patient with initially underwent surgical gastrostomy and tumoral mass excision. The patient then received chemotherapy and radiotherapy and underwent jejunal interposition. Patients with achalasia underwent surgical esophagomyotomy. Conclusion: The presence of solid dysphagia, malnutrition, and an associated disease may alert physicians to the presence of ES.

Accessory Hepatic Lobe: A Rare Cause of Prehepatic Portal Hypertension in a Child

Sag, Elif,Cansu, Aysegul,Imamoglu, Mustafa,Cakir, Murat The Korean Society of Pediatric Gastroenterology 2018 Pediatric gastroenterology, hepatology & nutrition Vol.21 No.4

Accessory hepatic lobe is noted as and considered a rare disease in children. It can manifest with various symptoms and complications depending on the location, volume, type and position of the disease as presented on a child. The patient presented as a 14-month-old girl who was seen with a notable hepatosplenomegaly and portal hypertension. A diagnosis was made after taking an extensive medical history, observation and radiological examinations. The formal diagnosis was a prehepatic portal hypertension associated with accessory hepatic lobe.

Endoscopic Findings of Children with Familial Mediterranean Fever

Sag, Elif,Demir, Ferhat,Saygin, Ismail,Kalyoncu, Mukaddes,Cakir, Murat The Korean Society of Pediatric Gastroenterology 2018 Pediatric gastroenterology, hepatology & nutrition Vol.21 No.4

Purpose: Familial Mediterranean fever (FMF) is an auto inflammatory disease characterized by periodic fever, synovitis and serositis. Patients may be admitted to gastroenterology units due to gastrointestinal symptoms. In this study; we aimed to analyze endoscopic findings and diagnostic utility of endoscopic procedure in children with FMF. Methods: Patient with FMF that was performed endoscopy for the gastrointestinal symptoms were included to the study (39 of 164 patients, 53 procedure). A control group was randomly designed as age and gender matched four endoscopic procedures per one endoscopic procedure of patients with FMF (n=212). Results: No different was found between the patients and control group in esophagogastroscopy findings. However, the diagnosis of gastrointestinal pathology was made by esophagogastroscopy in 46.2% patients. Colonoscopic examination revealed that the frequency of inflammatory bowel disease (IBD) was higher in undiagnosed patients compared to both the control group (50.0% vs. 6.9%, p<0.05, odds ratio [OR]:13.4 and 95% confidence inteval [95% CI]: 2.1-84.3) and the patients under colchicine treatment (50.0% vs. 8.3%, p<0.05, OR: 11 and 95% CI: 0.8-147.8). Colonoscopic procedure that was made after the diagnosis was found to provide contribution by 16.7% in determining the etiology of the additional symptoms. Conclusion: Patients with FMF may be admitted to pediatric gastroenterology outpatient clinic prior to diagnosis or during the follow-up period. The frequency of IBD is high in undiagnosed patients with FMF. Endoscopic procedures may be helpful in these patients for the diagnosis accompanying mucosal lesions.

A Rare Cause of Recurrent Acute Pancreatitis in a Child: Isovaleric Acidemia with Novel Mutation

Sag, Elif,Cebi, Alper Han,Kaya, Gulay,Karaguzel, Gulay,Cakir, Murat The Korean Society of Pediatric Gastroenterology 2017 Pediatric gastroenterology, hepatology & nutrition Vol.20 No.1

Recurrent acute pancreatic attacks is a rare clinical condition (2-5% of all acute pancreatis) in children and is mainly idiopathic in most cases. Sometimes it may be associated with congenital anomalies, metabolic diseases or hereditary conditions. Isovaleric acidemia (IVA) is a rare autosomal recessive amino acid metabolism disorder associated with isovaleryl coenzyme A dehydrogenase deficiency presenting the clinical findings such metabolic acidosis with increased anion gap, hyperammonemia, ketonemia, hypoglycemia, "the odor of sweaty feet," abdominal pain, vomiting, feeding intolerance, shock and coma. Recurrent acute pancreatitis associated with IVA have been rarely reported. Herein; we report a child who admitted with recurrent acute pancreatic attacks and had the final diagnosis of IVA. Mutation analysis revealed a novel homozygous mutation of (p.E117K [c.349G>A]) in the IVA gene. Organic acidemias must kept in mind in the differential diagnosis of recurrent acute pancreatic attacks in children.

Liver Involvement in Children with Alpha-1 Antitrypsin Deficiency: A Multicenter Study

Cakir, Murat,Sag, Elif,Islek, Ali,Baran, Masallah,Tumgor, Gokhan,Aydogdu, Sema The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.2

Purpose: Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. Methods: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). Results: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. Conclusion: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.

Liver Involvement in Children with Αlpha-1 Antitrypsin Deficiency: A Multicenter Study

Murat Cakir,Elif Sag,Ali Islek,Masallah Baran,Gokhan Tumgor,Sema Aydogdu 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.2

Purpose: Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. Methods: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). Results: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. Conclusion: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.

Primary Immunodeficiencies in Children Initially Admitted with Gastrointestinal/Liver Manifestations

Murat Cakir,Nalan Yakici,Elif Sag,Gulay Kaya,Ayşenur Bahadir,Alper Han Cebi,Fazil Orhan 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.4

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5–204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy

Murat Cakir,Sukran Senyuva,Sibel Kul,Elif Sag,Ali Cansu,Fulya Balaban Yucesan,Serap Ozer Yaman,Asim Orem 대한소아소화기영양학회 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.2

Purpose: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. Methods: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. Results: All parameters of neurocognitive development and serum calcium (9.6±0.9 mg/dL vs. 10.4±0.3 mg/dL, p <0.05) and magnesium (2.02±0.27 mg/dL vs. 2.2±0.14 mg/dL, p <0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition (1.33±0.22 vs. 1.18±0.22, p <0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels ( p <0.05, r=0.381). Conclusion: Calcium supplementation may improve neurocognitive development in malnourished infants.

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy

Cakir, Murat,Senyuva, Sukran,Kul, Sibel,Sag, Elif,Cansu, Ali,Yucesan, Fulya Balaban,Yaman, Serap Ozer,Orem, Asim The Korean Society of Pediatric Gastroenterology 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.2

Purpose: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. Methods: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. Results: All parameters of neurocognitive development and serum calcium ($9.6{\pm}0.9mg/dL$ vs. $10.4{\pm}0.3mg/dL$, p<0.05) and magnesium ($2.02{\pm}0.27mg/dL$ vs. $2.2{\pm}0.14mg/dL$, p<0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition ($1.33{\pm}0.22$ vs. $1.18{\pm}0.22$, p<0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p<0.05, r=0.381). Conclusion: Calcium supplementation may improve neurocognitive development in malnourished infants.