Recurrent Infections and Immunodeficiency Caused by Severe Pancytopenia Associated with a Novel Life-Threatening Mutation in Hypoxia-Upregulated Protein 1.

HYOU1 encodes a protein from the endoplasmic reticulum chaperone proteins, expressed to protect cellular mechanisms from stress such as hypoxia, insufficient energy and excessive or insufficient substances, and to restore cell homeostasis. In this study, we report a novel pathogenic variant in HYOU1. The proband, the second patient with pathogenic variant in HYOU1, was a female born to consanguineous parents. A novel homozygous pathogenic variant in HYOU1 (NM_001130991.3: c.1456C>T; p.Arg486Cys) was identified, causing anemia, thrombocytopenia and severe panleukopenia and immunodeficiency in the second month of age, leading to consistent high-grade fever, regression of brain functions and recurrent infections; ultimately resulting in the patient expiring at three and half months of age. Both parents are heterozygous for this variant and have no issues related to this study.

A single-amino-acid in-frame deletion in CYP17A1 results in combined 17-hydroxylase and 17,20-lyase deficiency in an Iranian family despite the protein mutation site.

In this study, we detected homozygous mutations in the CYP17A1 gene (NM_000102.4:c.1053_1055delCCT; p.Leu353del; SCV001479329) in a 28-year-old female patient (46,XX) and her phenotypically female 30-year-old sister (46,XY) who had phenotypes consistent with combined 17-hydroxylase and 17,20-lyase deficiency. The phenotypes were not expected based on the location of the mutation in the CYP17A1 redox partner-binding site and a previous description of the same mutation linked with isolated 17,20-lyase deficiency.

Prevalence and predictive factors of transient and permanent congenital hypothyroidism in Fars province, Iran.

INTRODUCTION: There is no data on the number as well as the prevalence of congenital hypothyroidism (CH) in the Fars province. Hence, we designed this study to analyze the latest data and the possible predictive factors on transient and permanent CH in this province. METHOD: This cross sectional study is based on the Fars province screening data from 2013 to 2016. A total of 294,214 newborns were screened with 938 confirmed cases of CH, which were included in this study. After recall and completion of the missing data, follow-up data for 642 CH cases with thyroid stimulating hormone (TSH) concentrations and levothyroxine doses for ten outpatient visits and final transient vs. permanent CH diagnosis were included. RESULTS: The incidence rate was 1:313.66, and out of the 642 CH cases, 66.04 % had permanent CH, while 33.96 % had transient CH. TSH level trend during the outpatient visits were not statistically different between the two groups (P = 0.312). A cutoff point of > 2.25 levothyroxine µg/kg (sensitivity: 76.11 %, specificity: 58.52 %) at the third year and a TSH concentration of > 43.35 mIU/L at the venous sampling (initial TSH) (sensitivity: 31.66 %, specificity: 90.32 %) were the predictive factors for permanent CH. CONCLUSION: Fars province has one of the highest incidence rate of CH in Iran. Levothyroxine dose at the 3rd year and the 1st venous TSH sample are the predictive factors for permanent CH in the Iranian population; however, TSH concentrations during follow ups are unreliable predictors.

Elevated serum TSH concentrations are associated with higher BMI Z-scores in southern Iranian children and adolescents.

BACKGROUND: Subclinical hypothyroidism is defined as elevated TSH levels while T4 or FT4 levels are normal. Elevated TSH levels are linked with obesity in adults. In a recent meta-analysis in Iran, 6.1% of children below 18 had obesity. Due to the low number of studies on the subject in children we, designed the study to assess the relation between BMI Z-score and TSH levels in children and adolescence. METHOD: This cross-sectional study was performed in a pediatric endocrinology clinic in Shiraz. Children aged between 2 to 18 years that came to the clinic for routine growth assessment follow up from January till April 2018 were considered. 850 children including 365 boys and 485 girls were included. RESULTS: Prevalence of subclinical hypothyroidism is increased in higher BMI groups. 9.9, 13.8, 17.2 and 20.5% of underweight, healthy weight, overweight and obese had subclinical hypothyroidism respectively. Obese and overweight participants had higher odds of subclinical hypothyroidism than those who were not (OR:1.649, P = 0.010, CI95% 1.126-2.413). On the other hand, Subclinical hypothyroid participants had higher odds of overweight or obesity than those who were euthyroid (OR:1.650, P = 0.010, CI95% 1.128-2.413). When TSH is set as a dependent value, TSH level is increased (ß = 0.126, r = 0.125, P = 0.001) with an increase in BMI Z-score. When BMI Z-score is set as a dependent value, BMI Z-score is increased (ß = 0.113, r = 0.243, P = 0.001) with an increase in TSH level. CONCLUSION: BMI Z-score and elevated TSH levels are positively correlated however studies should be performed on establishing the causality.

Association of lipid profile and BMI Z-score in southern Iranian children and adolescents.

Background Heart disease has been the leading cause of death for decades in the US population. Dyslipidemia is the most important risk factor for cardiovascular disease (CVD), and it often starts during childhood. Methods This cross-sectional study was performed in a growth assessment clinic in the city of Shiraz to determine the relation between body mass index (BMI) and dyslipidemia among children and teenagers aged 2-18 years. Nine hundred and eighty-nine children including 422 boys and 567 girls were selected. Results Adjusted for age and gender, total cholesterol (TC) (r = 0.172, p = 0.000), low-density lipoprotein cholesterol (LDL-c) (r = 0.176, p = 0.000), non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.227, p = 0.000) and triglycerides (TG) (r = 0.253, p = 0.000) showed a significant positive correlation with BMI Z-score, and HDL-c showed a significant negative correlation with BMI Z-score (r = -0.131, p = 0.000). Adjusted for age and gender, overweight and obese children were 1.882 times more likely to have high TC levels (p = 0.009), 2.236 times more likely to have high non-HDL-c levels (p = 0.000) and 3.176 times more likely to have high TG levels (p = 0.000) in comparison with children who had a healthy weight. Obese children had the highest percentage of isolated TG dyslipidemia (23.1%) and underweight children had the highest percentage of isolated HDL dyslipidemia (15.6%). Conclusions There is a strong link between atherosclerotic cardiovascular disease (ASCVD) and the level of blood lipids and between blood lipids and BMI Z-score. The first step in preventing ASCVD is the reduction of blood lipids, preventing weight gain and loss of extra weight.