Mothers' lived experience of caring for children with inborn errors of amino acid metabolism.

BACKGROUND: Inborn errors of amino acid metabolism are chronic conditions that have many sequels. Mothers of these children are facing different challenges which are underdetermined. This study was done to explore lived experience of mothers caring for these children. METHODS: This is an interpretive phenomenology with van Manen's approach which has 6 steps. Data were gathered by convenience and purposeful sampling. Nine mothers with different experiences were interviewed and the interviews were audiotaped. RESULTS: Six final themes were revealed from the exploring mothers' experiences including the future tied to the past, psychosis in the shadow of a lost ideal child, rebellion and blaming, the ways of escaping difficulties, self-forgetting in the shadow of full-time care, passing difficulties in the duality of hope-hopelessness, caring in a continuum of isolation-socialization. CONCLUSION: Mothers have multiple challenges in taking care of their children, especially psychologically and financially. So, nurses must plan programs for helping mothers of children with inborn errors of amino acid metabolism to reduce the effects of disease on mothers and consequently the children and the whole family.

Molecular characterization of a large cohort of mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis study (IMPRESsion).

Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through reanalysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, 90 harbored novel variants, and 9 had copy number variations. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50]). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.

Identified PAH V230A and PAH V230I mutations in a family with diverse clinical presentations.

Phenylketonuria (PKU) is a hereditary disorder caused by phenylalanine hydroxylase enzyme (PAH) defects that might cause severe brain damage. The current main treatment, dietary management, can prevent the symptoms if commenced early. However, it has side effects if used for a long time. Additionally, some patients with mild hyperphenylalaninemia (mHPA), who has serum phenylalanine levels <360 µmol/L, do not require treatment. Since the correlation between genotype and metabolic phenotype has been demonstrated earlier, genotype-based detection of patients who do not need treatment might help with genetic counseling and choosing the most appropriate treatment option. In this study, we report an asymptomatic adult with mHPA who had never taken any medical intervention to control or lower her serum phenylalanine level (Phe). She had 179 µmol/L serum phenylalanine level and carried p.[V230A];[V230I] genotype. Her child was affected with phenylketonuria and had p.[V230A];[V230A] genotype. Both pathogenic variants detected in the asymptomatic adult with mHPA were computationally analyzed to assess their pathogenicity and the p.V230I pathogenic variant was demonstrated to be responsible for the mHPA phenotype in the asymptomatic adult detected in this study. The findings in this study could contribute to genetic counseling and treatment for families and individuals with p.[V2030I];[V230A] genotype.

Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial.

OBJECTIVES: This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. METHODS: According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. RESULTS: The two intervention groups' Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). CONCLUSIONS: The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. CLINICAL TRIAL REGISTRATION: www.IRCT.irIRCT20171122037571N1.

Effects of Trehalose Administration in Patients with Mucopolysaccharidosis Type III.

BACKGROUND AND AIM: Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disease (LSD) caused by a deficiency of lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs), mainly in the central nervous system. Trehalose has been proposed as a potential therapeutic agent to attenuate neuropathology in MPS III. We conducted a single-arm, open-label study to evaluate the efficacy of trehalose treatment in patients with MPS IIIA and MPS IIIB. METHODS: Five patients with MPS III were enrolled. Trehalose was administrated intravenously (15 g/week) for 12 weeks. Health-related quality of life and cognitive function, serum biomarkers, liver, spleen, and lung imaging were assessed to evaluate trehalose efficacy at baseline and trial end (week 12). RESULTS: TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients, and the mean scores for quality of life were increased after the intervention. Serum GAG levels were reduced in all treated patients (however, the differences were not statistically significant). Alanine aminotransferase (ALT) levels were reduced in all patients post-treatment (p=0.0039). The mean levels of aspartate transaminase (AST) were also decreased after 12 weeks of treatment with Trehalose. Decreased serum pro-oxidant-antioxidant balance and increased GPX activity were observed at the end of the study. Decreases in mean splenic length were observed, whereas the liver volume did not change. CONCLUSION: Improvements in health-related quality of life and serum biomarkers (GAGs, liver aminotransferase levels, antioxidant status), as well as liver and spleen size, were found following 3 months of trehalose administration in patients with MPS IIIA and MPS IIIB.

Tetrahydrobiopterin responsiveness in Phenylalanine hydroxylase deficient patients from North-east of Iran: Genotype-phenotype correlation, identification of a novel mutation and 7 new responsive genotypes.

Phenylalanine hydroxylase enzyme defects result in a hereditary metabolic disorder called phenylketonuria. Sapropterin (tetrahydrobiopterin) is one of the treatment strategies for this disorder. Even though a correlation between genotype and BH4 responsiveness was established by earlier studies, a subset of mutations often presented inconsistent responses and/or phenotypes. Different genetic background is one of the potential reasons for this fact. In this study, the genotype of a total of 34 PAH deficient patients from Khorasan-Razavi providence in the north-east of Iran was obtained. Among this patients, 21 individuals took the 24 h and 48 h BH4 loading test and if the result was positive, their Phenylalanine tolerance was assessed. It is the first study of its type in patients from Iran to evaluate genotype role in predicting the most probable responsive individuals. The known pathogenic variant p.R169P and the novel variant p. Leu72_Asp75delinsTyr were first classified as responsive.Seven genotypes were reported as responsive for the first time. All patients carrying at least one pathogenic variant, which was previously reported as BH4 responsive, respond to BH4. Three patients with p.L48S, p.R261Q and p.A309V pathogenic variants were exceptions. There was no certain statistical correlation between genotype and response. Genotype and phenotype were significantly correlated and majority of patients with mild phenotype carried at least one non-null pathogenic variant. In Khorasan-Razavi province of Iran, patients with at least one non-null mutation are most probable to demonstrate mild phenotype and respond to BH4 phenotype.

Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.

BACKGROUND: Hyperphenylalaninemia (HPA) is the most common inborn error of amino acid metabolism worldwide. At least 2% of HPA cases are caused by a deficiency in tetrahydrobiopterin (BH4) metabolism. Genes such as QDPR and PTS are essential in the BH4 metabolism. This study aims to identify disease-causing variants in HPA patients, which may be helpful in genetic counseling and prenatal diagnosis. METHODS: A total of 10 HPA patients were enrolled in this study. The coding and adjacent intronic regions of PTS and QDPR genes were examined using Sanger sequencing. Protein modeling was also performed for novel identified variants. RESULTS: Ten patients and a total of 20 alleles were studied, which led to the identification of 10 different variants. All variants identified in PTS and QDPR were missense, except for the c.383_407del variant in the QDPR. Also, three novel variants were identified in the QDPR, including c.79G>T, c.383_407del and c.488G>A, and a novel variant, c.65C>G, in the PTS. CONCLUSIONS: Despite the genetic similarities in the disease-causing variants, differences were observed in the Asian and European populations with our populations; As a result, similar but more extensive studies are needed to investigate the distribution of disease-causing variants in genes involved in non-PKU hyperphenylalaninemia.

Impact of Intravenous Trehalose Administration in Patients with Niemann-Pick Disease Types A and B.

BACKGROUND AND AIMS: Niemann-Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the SMPD1 gene, resulting in progressive pathogenic accumulation of lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients. METHODS: Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12). RESULTS: The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients. CONCLUSIONS: Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored.

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Objective: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI. Methods: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients. Results: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D. Conclusion: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.

Genotyping of ABCC8, KCNJ11, and HADH in Iranian Infants with Congenital Hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is a heterogeneous disease with various underlying genetic causes. Among different genes considered effective in the development of CHI, ABCC8, KCNJ11, and HADH genes are among the important genes, especially in a population with a considerable rate of consanguineous marriage. Mutational analysis of these genes guides clinicians to better treatment and prediction of prognosis for this rare disease. The present study aimed to evaluate genetic variants in ABCC8, KCNJ11, and HADH genes as causative genes for CHI in the Iranian population. METHODS: The present case series took place in Mashhad, Iran, within 11 years. Every child who had a clinical phenotype and confirmatory biochemical tests of CHI enrolled in this study. Variants in ABCC8, KCNJ11, and HADH genes were analyzed by the polymerase chain reaction and sequencing in our patients. RESULTS: Among 20 pediatric patients, 16 of them had variants in ABCC8, KCNJ11, and HADH genes. The mean age of genetic diagnosis was 18.6 days. A homozygous missense (c.2041-21G > A) mutation in the ABCC8 gene was seen in three infants. Other common variants were frameshift variants (c.3438dup) in the ABCC8 gene and a missense variant (c.287-288delinsTG) in the KCNJ11 gene. Most of the variants in our population were still categorized as variants of unknown significance and only 7 pathogenic variants were present. CONCLUSION: Most variants were located in the ABCC8 gene in our population. Because most of the variants in our population are not previously reported, performing further functional studies is warranted.

Optimal Frequency to Screen Celiac Disease amongst Patients with Type 1 Diabetes Mellitus: A Multicenter Study.

AIMS: Celiac disease (CD) is frequent amongst patients with type 1 diabetes mellitus (T1DM). Since there is a disagreement on the optimal interval and frequency to perform screening tests for CD among diabetic patients, this study aimed to evaluate these issues amongst patients with T1DM. METHODS: This retrospective cohort study was conducted in seven referral diabetic centers in different cities of Iran from January 2020 to January 2021. Data belonging to 106 patients who were affected by both T1DM and CD was collected. The time interval between CD diagnosis and diabetes (IBCD), the age of diabetes onset, and any associated diseases, symptoms, and family history of T1DM and CD were recorded and analyzed. RESULTS: Results show that 45% of the patients with CD were diagnosed during the first year of diabetes onset; furthermore, 18% and 16% of the patients with CD were diagnosed in the second or third year after being diagnosed with diabetes. In addition, another 18% of patients with CD were diagnosed during the fourth till the eighth year after diabetes onset. Moreover, there was a negative relationship between the age of T1DM diagnosis and IBCD. Most participants were asymptomatic at the time of CD diagnosis. CONCLUSIONS: Screening tests to detect CD amongst patients with T1DM should continue for at least eight years after the initial T1DM diagnosis, especially those affected at a younger age.

Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus.

Background: Pompe disease, also denoted as acid maltase or acid α-glucosidase deficiency or glycogen storage disease type II, is a rare, autosomal recessive lysosomal storage disorder. Several reports have previously described Pompe disease in Iran and considering increased awareness of related subspecialties and physicians, the disease's diagnosis is growing. Objective: This guideline's main objective was to develop a national guideline for Pompe disease based on national and international evidence adapting with national necessities. Methods: A group of expert clinicians with particular interests and experience in diagnosing and managing Pompe disease participated in developing this guideline. This group included adult neurologists, pediatric neurologists, pulmonologists, endocrinologists, cardiologists, pathologists, and physiatrists. After developing search terms, four authors performed an extensive literature review, including Embase, PubMed, and Google Scholar, from 1932 to current publications before the main meeting. Before the main consensus session, each panel member prepared an initial draft according to pertinent data in diagnosis and management and was presented in the panel discussion. Primary algorithms for the diagnosis and management of patients were prepared in the panel discussion. The prepared consensus was finalized after agreement and concordance between the panel members. Conclusion: Herein, we attempted to develop a consensus based on Iran's local requirements. The authors hope that disseminating these consensuses will help healthcare professionals in Iran achieve the diagnosis, suitable treatment, and better follow-up of patients with infantile-onset Pompe disease and late-onset Pompe disease.

Response to sapropterin hydrochloride (Kuvan®) in children with phenylketonuria (PKU): a clinical trial.

Background Phenylketonuria (PKU) is one of the most common types of inborn error of metabolism. The mainstay of therapy for PKU has been dietary phenylalanine (Phe) restriction. Sapropterin dihydrochloride has been shown to be effective in reducing Phe levels in PKU patients. Methods This study was a clinical trial performed in the pediatric endocrine clinic of Imam Reza Hospital, Mashhad, Iran. Results All children between 1 and 10 years of age with a diagnosis of PKU whose serum Phe levels were between 120 and 360 µmol/L, in Khorasan Razavi province in the north-east of Iran, were enrolled. Twenty-four patients were enrolled in the study. Intervention: A free diet for 72 h was allowed and then a 20-mg/kg/day dose of Kuvan® was administered. More than 30% reduction in blood Phe levels was described as responsive. Eight patients responded to the loading test and were eligible for the second stage of the study. In this stage, Phe powder in combination with Kuvan was provided. Patients' serum Phe was measured weekly for 3 months. All eight patients showed Phe tolerance in 3 months, and their serum Phe levels remained within the range. Conclusions Treatment with Kuvan can help reduce blood Phe levels in our pediatric PKU population and allows patients to follow a more liberal diet.

Niemann-Pick Diseases: The Largest Iranian Cohort with Genetic Analysis.

OBJECTIVES: Niemann-Pick diseases (NPD) is an autosomal recessive inherited lysosomal lipid storage disorder which occurs due to a defect in cellular cholesterol trafficking, leading to excess lipid accumulation in multiple organ systems such as the brain, lungs, spleen, and liver. SPMD1-associated disease includes classic infantile and visceral NPD type A and B respectively. Type C NPD is subacute or juvenile. MATERIALS & METHODS: During 2012-2016, the patients who had the clinical and biochemical signs and symptoms of different types of NPD, underwent genetic analysis. All patients were collected from five provinces in Iran (Razavi Khorasan, South Khorasan, Khozaestan, Isfahan and Tehran province). Sanger sequencing of the candidate genes for NPD was performed followed by bioinformatics analysis to confirm the types of NPD and to identify novel mutations. All patients underwent full clinical assessment. RESULTS: We present two cases with NPD type A, six cases with NPD type B, and 11 cases with type C with various enzymatic defects identified in these cases. Within these 19 patients, we present 9 previously reported mutations and 10 novel mutations causing NPD. CONCLUSION: This study is the largest Iranian study for NPD analysis ever. Our report demonstrates that NPD has a variable age of onset and can present early in life. We investigated the clinical and genetic manifestations of a large Iranian cohort. Understanding the variable presentation of NPD will allow for clinicians to have a high index of suspicion for the disease.

Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing.

PURPOSE: Noonan Syndrome (NS) is an autosomal dominant disorder with many variable and heterogeneous conditions. The genetic basis for 20-30% of cases is still unknown. This study evaluates Iranian Noonan patients both clinically and genetically for the first time. MATERIALS/METHODS: Mutational analysis of PTPN11 gene was performed in 15 Iranian patients, using PCR and Sanger sequencing at phase one. Then, as phase two, Next Generation Sequencing (NGS) in the form of targeted resequencing was utilized for analysis of exons from other related genes. Homology modelling for the novel founded mutations was performed as well. The genotype, phenotype correlation was done according to the molecular findings and clinical features. RESULTS: Previously reported mutation (p.N308D) in some patients and a novel mutation (p.D155N) in one of the patients were identified in phase one. After applying NGS methods, known and new variants were found in four patients in other genes, including: CBL (p. V904I), KRAS (p. L53W), SOS1 (p. I1302V), and SOS1 (p. R552G). Structural studies of two deduced novel mutations in related genes revealed deficiencies in the mutated proteins. Following genotype, phenotype correlation, a new pattern of the presence of intellectual disability in two patients was registered. CONCLUSIONS: NS shows strong variable expressivity along the high genetic heterogeneity especially in distinct populations and ethnic groups. Also possibly unknown other causative genes may be exist. Obviously, more comprehensive and new technologies like NGS methods are the best choice for detection of molecular defects in patients for genotype, phenotype correlation and disease management.

Noonan syndrome - a new survey.

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available.

The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran.

Niemann-Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. The neurological involvement is typically proceeded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno-or hepatosplenomegaly in infancy or childhood). Early detection of NPC is important so that therapy with miglustat can delay onset of neurological symptoms and prolong survival. We describe here three infants from Birjand, South Khorasan, eastern Iran in 2016 with splenomegaly and different neurological signs that diagnosis was confirmed by genetic study. In all of them, NPC-509 was pathologically increased. They also had an unreported homozygous mutation (c.1415T>C, p.Leu472Pro) in exon 9 of the NPC1 gene. We found unreported homozygous mutation in NPC gene. Knowing this mutation is significant to our people. Genotype-phenotype correlations for this specific mutation needs to be further studied.

Non-thyroidal illness syndrome and cardiopulmonary bypass in children with congenital heart disease.

BACKGROUND: The thyroid hormones influence on all metabolic pathways. After heart surgery using cardiopulmonary bypass (CPB), serum T3 decreases and remains low for at least 24 hours. Several studies on pediatric have reported reduction of thyroid hormones after heart surgery. This study aimed to investigate the status of thyroid function tests in children with CPB surgery. METHODS: This study was carried out based on the available data on 132 children aged less than 15 years suffering from CHD. The patients underwent open heart surgery in Rajaie Center in Iran from January to November 2010. The thyroid hormone levels were measured shortly after admission, and postoperatively in Intensive Care Unit (ICU) and thereafter at 12, 24 and 48-hour intervals. The patients' gender, age, weight, body mass index, heart disease details, previous cardiac surgeries, and cardiac surgery-related data such as pump time, aortic clamping time, hypothermia duration, postoperative hemodynamic status and postoperative use of inotropic drugs were recorded and analyzed Results: All patients showed a decrease in T3, T4 and TSH and an increase in T3-resin uptake after surgery. Eventually, 3 (3.2%) patients died. Preoperatively, there was a significant association between the reduction in the thyroid hormone levels and inotropic drugs as well as the type of the heart disease (p<0.05). CONCLUSION: There is an association between post-operative inotropic drugs administration and reduction thyroid hormones levels in patients undergoing congenital heart disease cardiopulmonary bypass surgery.