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BACKGROUND: Chronic hepatitis B (CHB) remains an important global public health problem. Seroconversion is highly correlated with favourable long-term outcome. There is no consensus on the treatment method, onset time and duration for paediatric CHB patients. In this study, we aimed to evaluate the course of children with CHB, to determine the characteristics of the patients who developed spontaneous seroconversion and treatment indications, and to compare the effectiveness of different treatment modalities. PATIENTS AND METHODS: Patients aged 1-18 years with a diagnosis of CHB were included in this study and evaluated for the development of spontaneous hepatitis B envelope antigen (HBeAg)/surface antigen (HBsAg) seroconversion and treatment modalities. The treated patients were divided into two groups according to their treatment regimen. RESULTS: Of the 114 patients, the median age at diagnosis was 8.4 years and median follow-up period was 5.2 years. Spontaneous HBeAg and HBsAg seroconversion developed in 18 (20.6%) of 87 HBeAg positive patients and two (1.8%) patients, respectively. Thirty-one patients were treated. The follow-up period was higher in the group with HBeAg seroconversion (p:0.005). There was no statistical difference between the patients in terms of seroconversion development and treatment status. The serum alanine aminotransferase (ALT) values at the time of diagnosis were statistically higher in treated patients. CONCLUSION: HBV infection and CHB continue to be an important problem for children in our country. Consensus on the appropriate ALT ULN is needed for the treatment of hepatitis in children.
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Congenital diarrheal disorders (CDDs) are a heterogeneous group of inherited diseases that typically occur in the first weeks of life or can present later in life after the introduction of different nutrients; they can cause life-threatening severe dehydration and electrolyte disturbances. This study was conducted to characterize the causes of monogenic CDDs, and their clinical consequences. Clinical characteristics of 31 patients with CDDs that occurred in the first month of life and lasted more than 2 weeks were analyzed retrospectively. The patients were divided into groups according to the current CDD classification. The rate of consanguinity among parents was 77.4%. Of the patients, 16 (51.6%) were female and 15 (48.4%) were male. The underlying genetic defect was determined in 26 (83.9%) patients. The most common etiologic factors were digestive disorders of food and absorption and transport of electrolytes (58.1%, 18/31) (most of them being carbohydrate malabsorption disorders, 12/18) and intestinal immune system disorders (9.6%, 3/31). Total parenteral nutrition (TPN) was given to 45.2% (14/31) of the patients. Mortality rate was 28.5% (8/28). In conclusion, early diagnosis and treatment of CDDs with high morbidity and mortality is extremely important in terms of prognosis. Clinical and laboratory findings, stool characteristics, histopathological findings and the effects of dietary therapy are the primary and most important steps that lead to accurate diagnosis. In addition, advanced diagnostic possibilities, including genetic analyses, are essential for diagnosing underlying diseases.
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Diarreia , Doenças Raras , Carboidratos , Diarreia/diagnóstico , Diarreia/etiologia , Diarreia/terapia , Feminino , Humanos , Recém-Nascido , Masculino , Doenças Raras/complicações , Estudos RetrospectivosRESUMO
Disorders of intracellular trafficking are a group of inherited disorders, which often display multisystem phenotypes. Vacuolar protein sorting (VPS) subunit C, composed of VPS11, VPS18, VPS16, and VPS33A proteins, is involved in tethering of endosomes, lysosomes, and autophagosomes. Our group and others have previously described patients with a specific homozygous missense VPS33A variant, exhibiting a storage disease phenotype resembling mucopolysaccharidosis (MPS), termed "MPS-plus syndrome." Here, we report two siblings from a consanguineous Turkish-Arabic family, who have overlapping features of MPS and intracellular trafficking disorders, including short stature, coarse facies, developmental delay, peripheral neuropathy, splenomegaly, spondylar dysplasia, congenital neutropenia, and high-normal glycosaminoglycan excretion. Whole exome sequencing and familial segregation analyses led to the homozygous NM_022575.3:c.540G>T; p.Trp180Cys variant in VPS16 in both siblings. Multiple bioinformatic methods supported the pathogenicity of this variant. Different monoallelic null VPS16 variants and a homozygous missense VPS16 variant had been previously associated with dystonia. A biallelic intronic, probably splice-altering variant in VPS16, causing an MPS-plus syndrome-like disease has been very recently reported in two individuals. The siblings presented herein display no dystonia, but have features of a multisystem storage disorder, representing a novel MPS-plus syndrome-like disease, associated for the first time with VPS16 missense variants.
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Mucopolissacaridoses/genética , Mutação de Sentido Incorreto , Proteínas de Transporte Vesicular/genética , Anormalidades Múltiplas , Feminino , Homozigoto , Humanos , Lactente , Masculino , Mucopolissacaridoses/patologia , Linhagem , Fenótipo , Irmãos , SíndromeRESUMO
OBJECTIVES: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. METHODS: Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D (<0.02), intermediate (0.02-0.37) or normal (> 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. RESULTS: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients. CONCLUSIONS: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.
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Hepatopatias/etiologia , Doença de Wolman/diagnóstico , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Hepatopatias/fisiopatologia , Estudos Prospectivos , Turquia , Doença de Wolman/sangue , Doença de Wolman/fisiopatologia , Doença de WolmanRESUMO
Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase, which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine and urea. Herein we report a patient with arginase I (ARG1) deficiency who presented with recurrent nonconvulsive status epilepticus and liver failure. A novel homozygous frameshift mutation c.703_707delGGACTinsAGACTGGACC (p.G235Rfs*20) was detected.
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Arginase/genética , Hiperargininemia/complicações , Falência Hepática/etiologia , Estado Epiléptico/etiologia , Encéfalo/diagnóstico por imagem , Pré-Escolar , Feminino , Humanos , Hiperargininemia/diagnóstico por imagem , Hiperargininemia/genética , Falência Hepática/diagnóstico por imagem , Falência Hepática/genética , Imageamento por Ressonância Magnética , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/genéticaRESUMO
Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder caused by mutations in SLC5A1 encoding the apical sodium/glucose cotransporter SGLT1. We present clinical and molecular data from eleven affected individuals with congenital glucose-galactose malabsorption from four unrelated, consanguineous Turkish families. Early recognition and timely management by eliminating glucose and galactose from the diet are fundamental for affected individuals to survive and develop normally. We identified novel SLC5A1 missense variants, p.Gly43Arg and p.Ala92Val, which were linked to disease in two families. Stable expression in CaCo-2 cells showed that the p.Ala92Val variant did not reach the plasma membrane, but was retained in the endoplasmic reticulum. The p.Gly43Arg variant, however, displayed processing and plasma membrane localization comparable to wild-type SGLT1. Glycine-43 displays nearly invariant conservation in the relevant structural family of cotransporters and exchangers, and localizes to SGLT1 transmembrane domain TM0. p.Gly43Arg represents the first disease-associated variant in TM0; however, the role of TM0 in the SGLT1 function has not been established. In summary, we are expanding the mutational spectrum of this rare disorder.
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Erros Inatos do Metabolismo dos Carboidratos , Humanos , Células CACO-2 , Erros Inatos do Metabolismo dos Carboidratos/genética , Mutação , Glucose/metabolismo , Transportador 1 de Glucose-Sódio/genéticaRESUMO
BACKGROUND: Cerebroretinal microangiopathy with calcifications and cysts formerly known as Coats plus syndrome is a rare multisystemic autosomal recessive disease that affects the eyes, brain, bone, and gastrointestinal system. Intestinal telangiectasia are components of vascular malformations characterized by gastrointestinal system bleedings. Recurrent gastrointestinal system bleedings have been reported as being due to hepatic failure or vascular malformations of the gastrointestinal system tract. CASE: Here we report a patient who presented with recurrent gastrointestinal system bleeding episodes, bilateral exudative retinopathy, intracranial calcification and was diagnosed with Coats plus syndrome. Recurrent gastrointestinal system bleeding was controlled by monthly octreotide treatment. CONCLUSIONS: Coats plus syndrome presenting with vascular malformations should always be kept in mind in a patient with recurrent gastrointestinal bleeding and accompanying systemic physical findings. Octreotide treatment is an important option for patients with life threatening gastrointestinal system bleeding. Long term use of octreotide treatment can be used successfully in selected pediatric cases.
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Cistos do Sistema Nervoso Central , Malformações Vasculares , Ataxia , Neoplasias Encefálicas , Calcinose , Criança , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Leucoencefalopatias , Espasticidade Muscular , Octreotida/uso terapêutico , Doenças Retinianas , Convulsões , SíndromeRESUMO
BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. One of the disorders in PHTS spectrum, CS is characterized by macrocephaly, mucocutaneous findings, gastrointestinal system (GIS) polyposis and an increased lifetime risk of GIS, breast, thyroid and other cancers. CASE: In this study, we report an adolescent patient presenting with recurrent life-threatening upper GIS bleeding as a result of hamartomatous polyposis. Genetic studies revealed a known pathogenic nonsense mutation confirming the initial diagnosis of CS. CONCLUSIONS: Additionally, we describe our therapeutic intervention to improve the patient`s clinical symptoms with sirolimus, which its use is infrequently addressed in the literature for pediatric age group harboring PTEN mutations.
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Síndrome do Hamartoma Múltiplo , Adolescente , Criança , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndrome do Hamartoma Múltiplo/tratamento farmacológico , Humanos , Melena , PTEN Fosfo-Hidrolase/genética , Sirolimo/uso terapêutico , Glândula Tireoide/patologiaRESUMO
Iron deficiency anemia (IDA) is frequent in childhood. Inadequate nutrition and gastrointestinal malabsorption are the frequent causes of IDA in children. But reduced iron absorption and insidious blood loss from the gastrointestinal tract has been identified as the most frequent causes of IDA in older children and adolescents. Therefore the authors evaluated the frequency and etiologies of the upper gastrointestinal system pathologies causing IDA in older pediatric population. Patients with known hematological or chronic diseases, heavy menstrual flow, and obvious blood loss were excluded from the study. Forty-four children between the ages of 9.5 and 17.5 years and diagnosed with IDA were enrolled. They underwent upper gastrointestinal endoscopy and biopsy from esophagus, stomach, and duodenum. Mean age and hemoglobin (Hb) levels of study group (32 boys, and 12 girls) were 14.6 ± 2.0 years and 7.9 ± 1.8 g/dL, respectively. Only 1 patient had a positive serology testing with anti-tissue transglutaminase and small bowel biopsy correlating with celiac disease. Endoscopy revealed abnormal findings in 25 (56.8%) patients (21 endoscopic antral gastritis, 2 active duodenal ulcers, and 2 duodenal polyps). Helicobacter pylori (HP) infection was identified by using antral histopathological evaluation in 19 of 44 children (43.2%). In 2 of duodenal samples, one patient had celiac disease, and the other one was diagnosed as giardiasis. In conclusion, there are different etiologies resulting in IDA in older children and adolescents. When older children and adolescents are found to have iron deficiency, HP infection and other gastrointestinal pathologies should be ruled out before iron deficiency treatment.
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Anemia Ferropriva/diagnóstico , Endoscopia Gastrointestinal/métodos , Adolescente , Animais , Criança , Humanos , MasculinoRESUMO
BACKGROUND: Transaldolase (TALDO) deficiency (OMIM #606003) is a rare autosomal recessive multi-systemic disorder of carbohydrate metabolism. It has a vast phenotypic spectrum ranging from neonatal liver failure to slowly progressive liver cirrhosis and is characterized by intrauterine growth restriction, hepatosplenomegaly, bicytopenia, nephrolithiasis, and congenital heart disease. METHODS AND RESULTS: We report a patient with a late-onset form of TALDO deficiency characterized by hypergonadotropic hypogonadism and slightly elevated levels of alpha-fetoprotein (AFP). A novel TALDO1 mutation was detected through the application of reverse genetics with the use of clinical exome sequencing (CES). CONCLUSION: This report provides further evidence that reverse genetics is a useful approach in patients who do not manifest the hallmark features of known and recognizable syndromes. TALDO deficiency should be considered in the differential diagnosis of unexplained elevated AFP levels and hypergonadotropic hypogonadism with microlithiasis.
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Erros Inatos do Metabolismo dos Carboidratos , Hipogonadismo , Via de Pentose Fosfato/genética , Transaldolase/deficiência , Adolescente , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/genética , Masculino , Mutação , Transaldolase/genética , alfa-FetoproteínasRESUMO
OBJECTIVES: The aim of this study was to investigate the effect of Helicobacter pylori (H. pylori) infection on choroidal thickness (CT), retinal nerve fiber layer (RNFL) thickness, and ganglion cell (GCL+IPL) complex thickness in childhood cases of gastritis. METHODS: A total of 104 eyes of 52 children were included in the study. Two groups were created: 54 eyes of 27 H. pylori gastritis cases (Group 1) and 50 eyes of 25 gastritis without H. pylori cases (Group 2), as confirmed by an endoscopic biopsy. The mean subfoveal, submacular, and peripapillary CT, RNFL thickness, and GCL+IPL complex thickness was measured using spectral domain optical coherence tomography. RESULTS: The mean subfoveal CT values were significantly higher in Group 1 compared with Group 2 (p=0.042). The mean submacular CT and peripapillary CT measurements of the eyes in Group 1 was greater than that of Group 2, but the difference was not statistically significant (p>0.05). There was also no statistically significant difference between the GCL+IPL complex or RNFL thickness values of the groups (p>0.05). CONCLUSION: H. pylori is a common gastrointestinal infectious agent with asymptomatic carriers in the population. The role of this agent in ocular pathologies in adult patients has been the subject of many recent studies, but secondary ocular findings in patients with H. pylori gastritis in childhood have not yet been investigated. The results of this study showed that the subfoveal CT value was significantly greater in children with H. pylori gastritis.
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Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells. Single-cell RNA-sequencing analysis in a GIMAP5-deficient mouse model reveals replacement of LSECs with capillarized endothelial cells, a reduction of macrovascular hepatic endothelial cells, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC specification. Thus, GIMAP5 is a critical regulator of liver endothelial cell homeostasis and, when absent, produces portal hypertension. These findings provide new insight into the pathogenesis of portal hypertension, a major contributor to morbidity and mortality from liver disease.
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Células Endoteliais/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Homeostase/fisiologia , Hipertensão Portal/metabolismo , Fígado/metabolismo , Adolescente , Adulto , Animais , Feminino , Hepatócitos/metabolismo , Humanos , Cirrose Hepática/metabolismo , Masculino , Camundongos , Adulto JovemRESUMO
Jeune syndrome or asphyxiating thoracic dystrophy is a rare autosomal recessive skeletal dysplasia characterized by a small thorax, short-limbed dwarfism, renal and hepatic anomalies. It is estimated to occur in 1 per 100.000-130.000 live births. Radiological confirmation of diagnosis is essential. Prognosis of the disease is due to the severity of chest deformities and most of the patients are lost in their first year because of respiratory problems. We presented a 19-month-old female patient who admitted to our clinic because of recurrent lower respiratory tract infections and diagnosed as Jeune syndrome and reported due to its rarity.
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Asfixia/patologia , Osteocondrodisplasias/patologia , Infecções Respiratórias/etiologia , Doenças Torácicas/patologia , Tórax/anormalidades , Anormalidades Múltiplas , Asfixia/diagnóstico por imagem , Feminino , Genes Recessivos , Humanos , Lactente , Osteocondrodisplasias/diagnóstico por imagem , Prognóstico , Radiografia , Recidiva , Infecções Respiratórias/epidemiologia , Síndrome , Doenças Torácicas/diagnóstico por imagemRESUMO
PURPOSE: To assess the early changes of corneal and lens density in a pediatric population with celiac disease. METHODS: One hundred one patients were included in this observational and prospective study. Patients with celiac disease formed the celiac disease group. Healthy individuals with no medical history formed the control group. Corneal and lens density were assessed with Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany). RESULTS: The mean lens and corneal density outcomes in all zones did not differ between groups (P > .05 for each). Maximum lens density outcome was significantly higher in the celiac disease group than in the control group (P = .028). The mean corneal density at the peripheral cornea was significantly higher in females than males in the celiac disease group (P < .05 for each). Compliance with a gluten-free diet, body mass index, and histological classification of celiac disease had no significant effect on lens and corneal density in patients with celiac disease (P > .05 for each). CONCLUSIONS: Celiac disease did not affect the mean lens and corneal density in this pediatric population, but higher maximum lens density in patients with celiac disease and higher peripheral corneal density in female patients with celiac disease may indicate early stages of ocular involvement of celiac disease. [J Pediatr Ophthalmol Strabismus. 2019;56(6):402-406.].
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Doença Celíaca/complicações , Córnea/patologia , Doenças da Córnea/diagnóstico , Topografia da Córnea/métodos , Doenças do Cristalino/diagnóstico , Cristalino/patologia , Microscopia com Lâmpada de Fenda/métodos , Doença Celíaca/diagnóstico , Criança , Doenças da Córnea/etiologia , Progressão da Doença , Feminino , Humanos , Doenças do Cristalino/etiologia , Masculino , Estudos Prospectivos , Refração OcularRESUMO
PURPOSE: To investigate the effect of copper accumulation on corneal and lens clarity in children with Wilson disease (WD) compared to healthy children. METHODS: This multicenter cross-sectional study included 24 subjects with WD and 25 age-matched controls. Clinical and laboratory characteristics of the WD subjects were recorded. The Pentacam HR imaging system was used both for lens densitometry and corneal densitometry. RESULTS: Corneal densitometry values were higher in the posterior 6-10 mm (P = 0.021), posterior 10-12 mm (P < 0.001), posterior total diameter (P = 0.037), total thickness 10-12 mm (P = 0.032), and total thickness 6-10 mm zones and layers (P = 0.040) in the WD eyes than in control eyes. The lens densitometry values of zone 1 were higher in WD eyes (P < 0.001). There was a significant relationship between corneal densitometry values in the posterior 10-12 mm zones (P = 0.012; r = 0.527) and the duration of WD and liver copper content (P = 0.016; r = 0.507). A statistically significant correlation was also detected between lens densitometry values in zone 1 and WD duration (P = 0.018; r = 0.426). CONCLUSION: In this study cohort, children with WD had decreased corneal and lens clarity even in cases without Kayser-Fleischer rings and sunflower cataracts. Densitometry measurements using Scheimpflug imaging provided detection of corneal and lens involvement in the early stages of WD.
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Córnea/patologia , Topografia da Córnea/métodos , Densitometria/métodos , Degeneração Hepatolenticular/diagnóstico , Cristalino/patologia , Adolescente , Criança , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos ProspectivosRESUMO
Undiagnosed liver disease remains an unmet medical need in pediatric hepatology, including children with high gamma-glutamyltransferase (GGT) cholestasis. Here, we report whole-exome sequencing of germline DNA from 2 unrelated children, both offspring of consanguineous union, with neonatal cholestasis and high GGT of unclear etiology. Both children had a rare homozygous damaging mutation (p.Arg219* and p.Val204Met) in kinesin family member 12 (KIF12). Furthermore, an older sibling of the child homozygous for p.Val204Met missense mutation, who was also found to have cholestasis, had the same homozygous mutation, thus identifying the cause of the underlying liver disease. Conclusion: Our findings implicate rare homozygous mutations in KIF12 in the pathogenesis of cholestatic liver disease with high GGT in 3 previously undiagnosed children.
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Pâncreas/patologia , Pancreatite/diagnóstico , Doença Aguda , Criança , Feminino , Humanos , Isovaleril-CoA Desidrogenase/genética , Mutação de Sentido Incorreto , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Pancreatite/diagnóstico por imagem , Pancreatite/genética , Recidiva , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodosRESUMO
BACKGROUND: To find out if transabdominal ultrasonography (US) may have a predictive role for detection of antral gastritis and Helicobacter pylori (HP) infection in the antrum of pediatric age group. METHODS: A total of 91 (63.6%) patients and 52 (36.4%) controls were allocated into two groups as follows: Group 1 (n=91): patients with complaints and endoscopic findings consistent with gastritis and documented HP infection; Group 2 (n=52): patients with complaints and endoscopic findings consistent with gastritis in the absence of documented HP infection. These two groups were compared in terms of demographics and biggest mesenteric lymph node detected, muscularis mucosa thickness, submucosal thickness, muscularis propria thickness, and total gastric wall thickness. RESULTS: The two groups exhibited no statistically significant difference with respect to age (P=0.747), and presenting symptoms (P=0.982). However, the mesenteric lymph node dimension was significantly increased in Group 1 (P=0.039). Median mesenteric lymph node dimension was 12.9 (±15.4) mm in Group 1, while 11.0 (±12.8) mm in Group 2. No significant difference was observed between groups in terms of muscularis mucosa thickness (P=0.243), submucosal thickness (P=0.174), muscularis propria thickness (P=0.356), and total gastric wall thickness (P=0.223). CONCLUSIONS: Antral gastritis caused by HP infection in the pediatric age group is associated with increased mesenteric lymph node dimension observed by US.