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Background/aim: Therapeutic plasma exchange (TPE) is an extracorporeal treatment method that removes large molecular weight substances from plasma. In our study, we aimed to retrospectively examine the indications and procedural methods of the patients who had undergone TPE, and the complications that occurred during the procedure. Materials and methods: Forty-one patients who were monitored in thePICU of Gazi Yasargil Training and Research Hospital and had indications for TPE between 2017 and 2021 were included in the study. Laboratory parameters were checked before and after the TPE procedure. In addition to these, patients' diagnosis, weight, type of procedure and type of device, where the procedure was performed, duration of the procedure, amount of blood and plasma processed, complications, number of procedures, and death during the procedure or independent of the procedure were evaluated. Results: The median age was 93.0 (14.0-167.0) months. Hemolytic uremic syndrome (HUS) was the most common TPE indication with nine patients. The most common complication related to TPE was fever (11 patients), while no complication was observed in 18 patients.When laboratory results were evaluated according to American Society for Apheresis (ASFA) categories, a significant improvement was observed in the values of platelet, AST, ALT, LDH, urea, and creatinine in ASFA1 after TPE. No significant improvement was observed in ASFA2 (p > 0.05). In ASFA3, a significant improvement was observed in INR, AST, ALT, LDH, total bilirubin, creatinine, pH, and lactate values after TPE (p < 0.05). Five patients died from ASFA1, one from ASFA2, and three patients from ASFA3. Conclusion: Since significant adjustments are observed in clinical and laboratory values in sepsis-MOF, which is in the ASFA3 category, we believe that it should be evaluated in the ASFA2 or ASFA1 category in the early treatment of these diseases. In addition, we think that MIS-C cases, which have not been in any category according to ASFA, should be included in the ASFA2 or ASFA3 category, considering our TPE results.
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Unidades de Terapia Intensiva Pediátrica , Plasmaferese , Humanos , Plasmaferese/métodos , Feminino , Criança , Masculino , Estudos Retrospectivos , Pré-Escolar , Lactente , Adolescente , Síndrome Hemolítico-Urêmica/terapia , Resultado do TratamentoRESUMO
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.
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Diabetes Mellitus , Hipertrigliceridemia , Lipodistrofia Generalizada Congênita , Lipodistrofia , Infarto do Miocárdio , Insuficiência Renal Crônica , Feminino , Humanos , Turquia/epidemiologia , Estudos de Coortes , Infarto do Miocárdio/complicações , Insuficiência Renal Crônica/complicações , Estimativa de Kaplan-Meier , Hipertrigliceridemia/complicaçõesRESUMO
Early puberty signs lead to an increase in anxiety levels of parents and children. The aim of this study was to investigate the quality of life and anxiety levels of girls and their mothers who were admitted to a pediatric endocrinology clinic with concerns about early puberty. Girls and their mothers who were admitted to endocrinology outpatient clinic with concerns about early puberty were compared to healthy control group. Screen for Child Anxiety Related Emotional Disorders (SCARED) parent form, Quality of Life for Children Scale (PedsQL) parent form, and Beck Anxiety Inventory (BAI) were administered to the mothers. Children were evaluated with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS Lifetime Version) (K-SADS-PL). The study sample consisted of 92 girls and 62 of them were administered to clinic with concerns about early puberty. There were 30 girls in early puberty group (group 1), 32 girls were in the normal development group (group 2), and 30 were in the healthy control group (group 3). The anxiety level of group 1 and group 2 was significantly higher, and their quality of life was significantly lower when compared to group 3 (p < 0.001). Mother's anxiety level was found significantly higher in group 2 (p < 0.001). It has shown that anxiety level and quality of life of children were associated with anxiety level of mothers and the current Tanner stage (r = 0.302, p < 0.005). Conclusion: Mothers and children who have concerns about early puberty are negatively affected when early puberty is a possibility. For this reason, educating parents will prevent negative impacts of this situation on children. At the same time, it will decrease health burden. What is Known? ⢠Early adolescence is one of the most common reasons for admission to pediatric endocrinology outpatient clinics. It is known that increasing early adolescence anxiety in the society causes cost and time losses in the field of health. However, studies investigating the reasons for this result are limited in the literature. What's New? ⢠The level of anxiety increased significantly in girls with suspected precocious puberty and their mothers, and their quality of life was affected. ⢠For this reason, we would like to emphasize the importance of multidisciplinary approaches before psychiatric disorders occur in children with suspected precocious puberty and their parents.
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Transtornos Mentais , Puberdade Precoce , Feminino , Adolescente , Criança , Humanos , Mães/psicologia , Qualidade de Vida , Puberdade Precoce/diagnóstico , Ansiedade/diagnóstico , Ansiedade/etiologia , PuberdadeRESUMO
BACKGROUND: Classic galactosemia (CG) is a rare hereditary disease that can cause serious morbidity and death if it is not diagnosed and treated in early periods of life. Clinical findings usually occur in the neonatal period after the neonate is fed with milk that contains galactose. Most patients are presented with jaundice, hepatomegaly, hypoglycemia and cataracts. OBJECTIVE: We aimed to document the clinical, molecular characteristics, regional estimated incidence and time of diagnosis in newborn with CG. MATERIALS AND METHOD: The data of 63 newborn with CG who were diagnosed and followed up between January 2011 and January 2018 were analyzed retrospectively. RESULTS: During the study period, 63 (33 boys and 30 girls) newborns were diagnosed with CG. The median gestational age was 39 weeks (33-42). Major presenting symptoms were jaundice 90.5% and cataract 41.2%. The mean age at first symptom was 12 ± 7.4 days while the mean age at diagnosis was 18.9 ± 10.6 days. Nearly half of the patients (55.5%) were diagnosed later than the postnatal 15th day. Genetic analysis was performed on 56 patients and homozygous Q188R mutation was found in 92.8%. There were signs of sepsis in 33.3% of the cases. Six patients died due to sepsis. There was consanguinity in 84.1% of the parents and regional estimated incidence was calculated as 1 in 6103 live births. CONCLUSION: Q188R mutation was found in 92.8% of our cases. The regional estimated incidence was found as 1 in 6103 live births. Our study strongly supports that galactosemia should be included in the national newborn screening program.
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Galactosemias , Sepse , Masculino , Feminino , Humanos , Recém-Nascido , Lactente , Galactosemias/diagnóstico , Galactosemias/epidemiologia , Galactosemias/genética , Estudos Retrospectivos , Triagem Neonatal , MutaçãoRESUMO
Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes presenting within the first 6 months of life. INS gene promoter mutations have been shown to cause both remitting/relapsing and permanent NDM. We, herein, present three interesting patients with INS gene promoter mutations. Two cousins with an identical homozygous c.-331C > G mutation presented with NDM. The first cousin had nonremitting diabetes and still requires multidose insulin injections at the current age of 6.1 years. However, the other cousin's diabetes remitted at the age of 9 months, and she is still in remission at the age of 3 years with no medication or dietary intervention required (latest HbA1c was 4.9%). The third patient had NDM also due to a homozygous INS promoter c.-331C>A mutation. Her diabetes remitted at the age of 2 months and relapsed at the age of 2.6 years with severe diabetic ketoacidosis (DKA). Distinct clinical phenotype and relapse with severe DKA in one of the three cases suggest that INS promotor mutations can cause a heterogeneous phenotype and even cases exhibiting remission can relapse unpredictably. Therefore, as the age of relapse is unpredictable, close follow-up and family education on diabetes symptoms are essential for cases with remitting/relapsing diabetes due to INS gene mutations.
Assuntos
Diabetes Mellitus/genética , Insulina/genética , Mutação/genética , Regiões Promotoras Genéticas/genética , Feminino , Humanos , Recém-Nascido , Linhagem , Fenótipo , Recidiva , Remissão EspontâneaRESUMO
Several recent studies have reported that toxic metabolites accumulated in the body as a product of inborn errors of metabolism (IEM) are eliminated more rapidly with continuous venovenous hemodiafiltration (CVVHDF) than with peritoneal dialysis (PD). However, there is still uncertainty about the impacts of dialysis modalities on the short-term outcome. Here, it was aimed to investigate the effects of dialysis modalities on the short-term outcome. This retrospective study included 40 newborn infants who underwent PD (29 patients) or CVVHDF (11 patients) due to inborn errors of metabolism at a tertiary centre, between June 2013 and March 2018. The outcomes and the potential effects of the dialysis modality were evaluated. Of 40 patients, 21 were urea cycle defect, 14 were organic academia, and 5 were maple syrup urine disease. The median 50% reduction time of toxic metabolites were shorter in patients treated with CVVHDF (p < 0.05). Catheter blockage was the most common complication observed in PD group (24.1%), whereas in CVVHDF group hypotension and filter blockage were more common. There was no significant difference in mortality between dialysis groups (38% vs. 45.4%, p > 0.05). In patients with hyperammonaemia, duration of plasma ammonia > 200 µg/dL was the most important factor influencing mortality (OR 1.05, CI 1.01-1.09, p = 0.007).Conclusion: This study showed that CVVHDF is more efficient than PD to rapidly eliminate toxic metabolites caused by IEM in newborn infants, but not in improving survival. What is Known: â¢Toxic metabolites are eliminated more rapidly with CVVHDF than with PD. â¢Higher complication rates were reported with rigid peritoneal catheters in PD and catheter blockage in CVVHDF. What is New: â¢Prolonged duration of plasma ammonia levels above a safe limit (200 µg/dL) was associated with increased mortality. â¢Lower catheter-related complication rates may have been associated with the use of Tenckhoff catheters in PD and the use of right internal jugular vein in CVVHDF.
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Amônia/sangue , Hemodiafiltração/mortalidade , Erros Inatos do Metabolismo/terapia , Diálise Renal/mortalidade , Amônia/farmacocinética , Feminino , Hemodiafiltração/métodos , Humanos , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/mortalidade , Diálise Renal/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.
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Cariótipo Anormal , Antropometria , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Fenótipo , Adulto JovemRESUMO
Neonatal-onset propionic acidemia (PA), the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, and can progress to coma if not identified and treated appropriately. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Herein, we report a case of 3-day-old neonate with PA presented with acute renal failure and metabolic acidosis was effectively treated by peritoneal dialysis and conventional methods.
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Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Hiperamonemia/etiologia , Hiperamonemia/terapia , Acidemia Propiônica/complicações , Acidemia Propiônica/terapia , Terapia Combinada , Feminino , Humanos , Recém-Nascido , Diálise Peritoneal , Acidemia Propiônica/diagnósticoRESUMO
Haloperidol is commonly used in the treatment of psychiatric disorders. Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. For the first time, we report a neonate with transient nephrogenic diabetes insipidus (DI) caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. Haloperidol can have adverse effects on the fetus and newborn infant, that's why one should prevent the use of haloperidol during pregnancy and lactation.
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Antipsicóticos/efeitos adversos , Diabetes Insípido Nefrogênico/induzido quimicamente , Haloperidol/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Adulto , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
OBJECTIVES: The mitochondrial elongation factor Tu (EF-Tu), encoded by the TUFM gene, is a GTPase, which is part of the mitochondrial protein translation mechanism. If it is activated, it delivers the aminoacyl-tRNAs to the mitochondrial ribosome. Here, a patient was described with a homozygous missense variant in the TUFM [c.1016G>A (p.Arg339Gln)] gene. To date, only six patients have been reported with bi-allelic pathogenic variants in TUFM, leading to combined oxidative phosphorylation deficiency 4 (COXPD4) characterized by severe early-onset lactic acidosis, encephalopathy, and cardiomyopathy. CASE PRESENTATION: The patient presented here had the phenotypic features of TUFM-related disease, lactic acidosis, hypotonia, liver dysfunction, optic atrophy, and mild encephalopathy. CONCLUSIONS: We aimed to expand the clinical spectrum of pathogenic variants of TUFM.
Assuntos
Fator Tu de Elongação de Peptídeos , Humanos , Acidose Láctica/genética , Mitocôndrias/genética , Mitocôndrias/patologia , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Proteínas Mitocondriais , Mutação , Mutação de Sentido Incorreto , Fator Tu de Elongação de Peptídeos/genética , PrognósticoRESUMO
This study aimed to determine the incidence of congenital hypothyroidism in Turkey's Diyarbakir Province and assess the development and growth conditions of people with congenital hypothyroidism. Patients born between 2011-2019 and diagnosed with congenital hypothyroidism within the scope of the newborn screening program were included. The medical records of these patients were retrospectively reviewed. The length and weight for age, weight for length, and body mass index standard deviation scores were calculated. We investigated the treatment status of the patients, whether their relatives had a similar disorder, and the presence of consanguinity between parents. Blood samples were collected from 380,592 newborns. As a result of further tests, 498 newborns were diagnosed with congenital hypothyroidism (incidence: 1/764). Demographic and anthropometric data of 241 patients were analyzed. The patients comprised 46.9% (nâ =â 113) females and 53.1% (nâ =â 128) males. It was determined that 44.4% of the individuals had transient congenital hypothyroidism and 53.6% had permanent congenital hypothyroidism. The parents of 29.8% of the individuals diagnosed with transient congenital hypothyroidism and 44.2% of the individuals diagnosed with permanent congenital hypothyroidism were consanguineous (Pâ =â .02). According to the latest anthropometric assessment, 6.8% of individuals diagnosed with congenital hypothyroidism had a weight z-score below -2 SD and 16.9% had a length z-score below -2 SD. The incidence of congenital hypothyroidism was higher in our region. The ratio of consanguinity between parents was higher in patients diagnosed with permanent congenital hypothyroidism than in those diagnosed with transient congenital hypothyroidism. According to the most recent follow-up, weight and age were found to be similar in patients with transient and permanent congenital hypothyroidism.
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Hipotireoidismo Congênito , Masculino , Feminino , Humanos , Recém-Nascido , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/epidemiologia , Triagem Neonatal , Turquia/epidemiologia , Estudos Retrospectivos , Testes de Função Tireóidea , TireotropinaRESUMO
OBJECTIVES: To evaluate the clinical characteristics and treatment options of neonates requiring prolonged hospitalization due to persistent hyperinsulinemic hypoglycemia (HH). METHODS: This retrospective cohort study included infants >34 weeks of gestation at birth who were born in our hospital between 2018 and 2021, diagnosed with HH, and required diazoxide within the first 28 days of life. The baseline clinical characteristics, age at the time of diagnosis and treatment options in diazoxide resistance cases were recorded. Genetic mutation analysis, if performed, was also included. RESULTS: A total of 32 infants diagnosed with neonatal HH were followed up. Among the cohort, 25 infants were classified as having transient form of HH and seven infants were classified as having congenital hyperinsulinemic hypoglycemia (CHI). Thirty-one percent of the infants had no risk factors. The median birth weight was significantly higher in the CHI group, whereas no differences were found in other baseline characteristics. Patients diagnosed with CHI required higher glucose infusion rate, higher doses, and longer duration of diazoxide treatment than those in the transient HH group. Eight patients were resistant to diazoxide, and six of them required treatment with octreotide and finally sirolimus. Sirolimus prevented the need of pancreatectomy in five of six patients without causing major side effects. Homozygous mutations in the ABCC8 gene were found in four patients with CHI. CONCLUSIONS: The risk of persistent neonatal hyperinsulinism should be considered in hypoglycemic neonates particularly located in regions with high rates of consanguinity. Our study demonstrated sirolimus as an effective treatment option in avoiding pancreatectomy in severe cases.
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Hiperinsulinismo Congênito , Diazóxido , Lactente , Recém-Nascido , Humanos , Diazóxido/uso terapêutico , Estudos Retrospectivos , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/tratamento farmacológico , Hiperinsulinismo Congênito/genética , Sirolimo/efeitos adversos , MutaçãoRESUMO
Congenital generalized lipodystrophy (CGL) is a rare, autosomal recessive disorder characterized by an almost complete absence of body fat. In CGL, patients may have hyperphagia due to leptin deficiency. Recombinant human leptin (metreleptin) has been suggested as an effective treatment option. We present successful treatment with metreleptin in a boy with CGL and results from the first year of follow-up. An eight-month-old boy presented with excessive hair growth and a muscular appearance. On examination he had hypertrichosis, decreased subcutaneous adipose tissue over the whole body and hepatomegaly. Laboratory investigations revealed hypertriglyceridemia, hyperinsulinemia, elevated liver transaminases and low leptin levels. Molecular genetic analysis detected a homozygous, c.465_468delGACT (p.T156Rfs*8) mutation in the BSCL2 gene. A diagnosis of CGL type 2 was considered. Despite dietary intervention, exercise, and treatment with additional omega-3 and metformin, the hypertriglyceridemia, hyperinsulinemia, and elevated liver transaminase levels worsened. Metreleptin treatment was started and after one year hyperphagia had disappeared, and there was dramatic improvement in levels of insulin, hemoglobin A1c, triglycerides and liver transaminases. Hepatosteatosis was lessened and hepatosplenomegaly was much improved. Metreleptin appears to be an effective treatment option in children with CGL that remarkably improved metabolic complications in the presented case. Initiation of metreleptin treatment in the early period may decrease mortality and morbidity, and increase the quality of life in children with CGL.
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Subunidades gama da Proteína de Ligação ao GTP , Hiperinsulinismo , Hipertrigliceridemia , Lipodistrofia Generalizada Congênita , Criança , Humanos , Lactente , Masculino , Subunidades gama da Proteína de Ligação ao GTP/genética , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Hiperinsulinismo/complicações , Hiperfagia/complicações , Hipertrigliceridemia/complicações , Leptina/genética , Leptina/metabolismo , Lipodistrofia Generalizada Congênita/tratamento farmacológico , Lipodistrofia Generalizada Congênita/genética , Lipodistrofia Generalizada Congênita/complicações , Mutação , Qualidade de VidaRESUMO
AIM: Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia, and alacrimia. This disorder is caused by mutations in the AAAS gene. The aim of this study is to discuss the clinical, laboratory and molecular genetic analysis results of 12 patients with TAS. METHOD: We evaluated 12 patients from 8 families. Clinical and laboratory data were retrospectively collected from the medical records of the patients in the database for the period 2015-2020. All exons and exon-intron junctions of the AAAS gene were evaluated by next-generation sequencing method. Detected variants were classified according to American Collage of Medical Genetics criteria. RESULTS: Alacrimia was found in all patients (100%); achalasia was found in 10 patients (83.3%) and adrenal insufficiency was found in 10 patients (83.3%). In addition, hyperreflexia(6/12), learning disability(5/12), hypernasal speech(5/12), muscle weakness(8/12), delayed walking(7/12), delayed speech(6/12), excessive sweating(7/12), optic atrophy(1/12), epilepsy(1/12), palmoplantar hyperkeratosis(5/12), multiple dental caries(9/12), atrophy of the thenar/hypothenar muscles(4/12) and short stature(4/12) were detected. The DHEA-S levels were measured in 10 patients and were found to be low in 8 of them. In all patients, the sodium and potassium levels were found to be normal. AAAS gene sequencing revealed four previously reported c.1066_1067del (p.Leu356fs*8), c.1432 C > T (p.Arg478*), c.688 C > T (p.Arg230*), and c.1368_1372del (p.Gln456fs*38) variants and two novel homozygous c.1250-1 G > A and c.398_399 + 2del variants in the AAAS gene. CONCLUSION: We detected two novel variants in the AAAS gene. While the classic triad is present in 66.7% of the cases, neurological dysfunction, skin and dental pathologies also occur quite frequently. The earliest and most common finding of TAS is alacrimia. Therefore, adrenal insufficiency should be investigated in all patients with alacrimia and if necessary, genetic analysis should be performed for TAS. In addition, TAS should be followed up with a multidisciplinary approach since it involves many systems.
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Insuficiência Adrenal , Cárie Dentária , Acalasia Esofágica , Humanos , Acalasia Esofágica/genética , Turquia/epidemiologia , Estudos Retrospectivos , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/genéticaRESUMO
Background: Cerebral organic acid disorders are progressive neurometabolic diseases characterized by neurologic dysfunction. Glutaric aciduria type I (GA-I) and L-2-hydroxyglutaric aciduria (L2HGA) are the main cerebral organic acid disorders. They are both classified as, and it is suggested that these two disorders may share a common metabolic pathway. Current treatment strategies are based on levocarnitine, vitamin B2, and diet. Recent guidelines recommend a lysine-restricted diet up to six years of age, but there is no consensus for patients over the age of six. Vitamin B2 is exists in the blood as riboflavin and its cofactors, flavin mononucleotide and flavin adenine dinucleotide (FAD). FAD, the cofactor of L2HGD, accelerates the conversion of L-2-hydoxy glutarate to alpha-ketoglutarate. Levocarnitine stimulates the formation and excretion of derivatives of glutaric acid. Also, lysine-associated organic acidurias some results provide principal proof for the beneficial effects of riboflavin in GA-I. It has been previously reported that combination therapy with riboflavin and levocarnitine is effective for L2HGA as well as GA-I. Riboflavin and levocarnitine have been reported to improve not only clinical symptoms but also urinary 2-HGA levels. In our study, we aimed to evaluate the effect of the current treatment strategies and genotype on urinary metabolites and IQ scores in GA-I and L2HGA patients. Methods: The presented retrospective multicenter study included patients followed up in Diyarbakir Children's Hospital and Izmir Katip Celebi University Faculty of Medicine, Division of Pediatric Metabolism. Between 2016 and 2021, we retrospectively evaluated 35 patients with confirmed diagnosis of GA-I and L-2HGA. We analyzed the clinical, biochemical, neuroradiological, molecular data and treatment of the patients. The follow-up period was every 2 months until 12 months old, every 3 months until 6 years of age, and every 6 months thereafter. Therapy monitoring was undertaken during follow-up visits that included evaluation of clinical parameters, laboratory parameters, and dietary consumption records. Denver II was applied in order to evaluate children aged 0-6 years in terms of development. Patients between 6 and 16 years of age were evaluated using the Wechsler Intelligence Scale for Children-Revised. Results: We identified 25 with GA-I and 10 with L2HGA. The most common clinical symptoms were developmental delay, intellectual disability, and movement disorders. Behavioural problems were more common in L2HGA than in GA-I patients. In the same family, there were patients with severe developmental delay despite early diagnosis and treatment and individuals with normal IQ scores. In our study group, we used diet (lysine restricted or protein controlled), levocarnitine and vitamin B2 for GA-I patients. The mean urinary glutaric acid levels were decreased with treatment in GA-I patients. Group I consisted of 14/25 patients receiving lysine restricted diet and levocarnitine, Group II (8/25) received protein-controlled diet and levocarnitine. Group III (3/25) patients whom had p.Pro248Leu (P248L) variant, received riboflavin in combination with protein-controlled diet and levocarnitine. When we evaluated according to the treatment groups, a significant decrease was observed in urinary glutaric acid levels in group I. But there were no significant difference in Group II and III. The patients with c.1018C > T variant in GCDH gene had higher pre-treatment urinary metabolites and significant reduction in urinary metabolites with treatment was detected. In L2HGA patients, we used levocarnitine and vitamin B2. In all L2HGA patients, there was a significant decrease in the mean urinary 2- hydoxy glutarate with treatment. However, there was no significant difference between the c.164G > A and c.1115delT variants. The mean pre- and post-treatment IQ scores of GA-I patients, no significant difference was observed. Relative neurologic improvement was seen in three L2HGA patients. We found two novel variants, including the c.221A > G (p.Tyr74Cys) in the GCDH gene and the c.738 + 5A > G splice variant in the L2HGDH gene. Conclusions: Glutaric aciduria type I and L2HGA are the most common cerebral organic acidurias. Early and correct diagnosis is crucial. Poor prognosis based on metabolic crises and progressive deterioration still appears. In countries where newborn screening is not performed, a clinical suspicion index is required for cerebral organic aciduria. GA-I and L-2HGA are difficult to examine by medical evidence standards because of the small sample size, regional differences in newborn screening, and medical care limits. More clinical studies are needed to identify effective treatments. However, the significant decrease in urinary glutaric acid levels after treatment in patients on lysine-restricted diet raises the question of whether lysine-restricted diet should be continued after six years of age. We also reported our experience in order to contribute to the literature.
RESUMO
BACKGROUND: Phenylketonuria (PKU) and biotinidase deficiency (BD) are autosomal recessive diseases. If they are not identified and treated early, severe intellectual disability and developmental delay occur. This study was conducted to calculate the ten-year incidence of PKU and BD in the Diyarbakir province of Turkey. METHODS: This cross-sectional study included patients born between 2011-2020 and diagnosed with PKU and BD. Patients with a clear diagnosis had their records evaluated retrospectively. RESULTS: Between 2011 and 2020, blood was taken from 417,525 newborns` heels in Diyarbakir province. As a result of further diagnostic testing, 53 PKU (Incidence: 1:7878) and 177 BD (Incidence: 1:2359) were detected. Of the patients with BD, 56% had profound BD and 44% had partial BD. The records of a total of 269 patients (PKU: 25; BD: 123; Hyperphenylalaninemia: 121) were examined. Parents of 65% (n=15) of the patients diagnosed with PKU and 46.6% (n=55) of the patients diagnosed with BD were consanguineous. CONCLUSIONS: The incidence of both PKU and BD was found to be high in our region. The high number of consanguineous marriages was regarded as the most important explanation for the high frequency of these illnesses.
Assuntos
Deficiência de Biotinidase , Fenilcetonúrias , Humanos , Recém-Nascido , Triagem Neonatal , Deficiência de Biotinidase/diagnóstico , Deficiência de Biotinidase/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Fenilcetonúrias/diagnóstico , Fenilcetonúrias/epidemiologiaRESUMO
Objective: The incidence of type 1 diabetes mellitus (T1D) in children has an increasing trend globally, with a variable rate depending on region and ethnicity. Our group first reported T1D incidence in Diyarbakir in 2011. The aim of this study was to evaluate the current incidence rate of pediatric T1D in Diyarbakir, and compare the incidence, and clinical and presenting characteristics of more recent cases with those reported in our first report. Methods: Hospital records of patients diagnosed with T1D in Diyarbakir city between 1st January 2020 and 31st December 2020 and aged under 18 years old were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI). Results: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age at diagnosis was 9.5±3.9 years (0.8-17.9). TSI data indicated a population count of 709,803 for the 0-18 years age group. Thus the T1D incidence was 8.03/105 in the 0-18 age group and was higher in the 0-14 age group at 9.14/105. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with diabetic ketoacidosis was 64.9%. Conclusion: The annual incidence of pediatric T1D in Diyarbakir city increased from 7.2/105 to 9.14/105 within the last decade. The rate of annual increase was 2.7% in the 0-14 age group comparing this study with our earlier report, with a predominance in male subjects and a shift of peak incidence from the 5-9 year age group in the first study to the 10-14 year age group in this one.
Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Adolescente , Idoso , Criança , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/etiologia , Feminino , Humanos , Incidência , Masculino , Turquia/epidemiologiaRESUMO
BACKGROUNDS: During the Coronavirus-19 disease (Covid-19) pandemic it was observed that the number of girls presenting with early puberty had increased. The aim of this study was to carry out a retrospective evaluation of the characteristics of girls who had been referred for evaluation of precocious puberty in five different pediatric endocrinology units, before and during the pandemic. METHODS: The study participants comprised 359 girls who were assigned into 2 groups a pre-pandemic group (n:214) and a pandemic group (n:145). Those participants (n:99) who had medical records in the follow-up period were classified into 3 subgroups according to the time of presentation and follow-up visits (group-1: first admission and follow-up visit before the pandemic, group-2: first admission before the pandemic, the follow-up visit during the pandemic, group-3: first admission and follow-up visit during the pandemic). RESULTS: The age at presentation and age at pubertal onset were both significantly lower in the pandemic group than those in the pre-pandemic group(8.1 vs 8.6, p: < 0.001,7.7 vs 7.9,p:0.013, respectively). There was no significant difference between the body mass index standard deviation scores (BMI-SDS) values of the groups (0.57 vs 0.51, p:0.430). The initiation rate of pubertal suppression therapy at the time of presentation was significantly higher in the pandemic group compared to that of the pre-pandemic group (7.7%vs 27.5%), and in groups-2 & 3 compared to group-1, during follow-up (20%&44%vs 8%). CONCLUSION: Our research showed that the onset of puberty occurred earlier in the pandemic period compared to the previous year, and the need for pubertal suppression therapy increased during the pandemic.
Assuntos
COVID-19 , Puberdade Precoce , COVID-19/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Pandemias , Puberdade , Puberdade Precoce/diagnóstico , Puberdade Precoce/epidemiologia , Estudos Retrospectivos , Turquia/epidemiologiaRESUMO
BACKGROUND: Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up. OBJECTIVE: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment. DESIGN AND METHOD: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses. RESULTS: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200â +â 1Gâ >â A, p.F130L, p.E198del, c.1122-18Gâ >â A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I. CONCLUSIONS: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.
Assuntos
Citocromo P-450 CYP11B2/deficiência , Citocromo P-450 CYP11B2/genética , Fludrocortisona/farmacologia , Hipoaldosteronismo/patologia , Mutação , Suspensão de Tratamento/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Hipoaldosteronismo/tratamento farmacológico , Hipoaldosteronismo/enzimologia , Lactente , Recém-Nascido , Masculino , PrognósticoRESUMO
It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.