Sib-pair subgroup familial type 1 diabetes mellitus in children in the state of Qatar.

BACKGROUND: Type 1 diabetes is the most common type of diabetes mellitus (DM) in children. It can be sporadic in onset or cluster in families, which comprises parent-offspring and sib-pair subgroups. The risk of developing DM in first-degree relatives of affected individuals is 8-15 fold higher. There is limited data about familial DM from the Gulf region. This study aims to describe the clinical, biochemical and genetic characteristics of sib-pair familial type 1 diabetes in Qatar. METHODS: Every child with DM following up at Sidra Medicine was recruited. Data was collected regarding clinical features, family history, type 1 diabetes autoantibodies and whole genome sequencing was performed. Genetic analysis for MODY genes and HLA association analysis was conducted. RESULTS: 44 families with sib-pair familial diabetes were identified. Of these, 2 families had 4 affected siblings and 5 families had 3 affected siblings. The majority are of Qatari ethnicity and the most common autoantibody was GAD65. The most common age of onset in the proband was 5-9 years while it was 10-14 years in subsequent siblings. The occurrence of DKA & HbA1c levels were lower in the second affected sibling. No relevant MODY gene variants were found. HLA analysis found 15 variants in at least 50% of the subjects. Most common were HLA-F*01*01*01G, HLA- DPA1*01*03*01G, HLA- DRB3*02*02*01G, HLA- E*01*01*01G & DRB4*03*01N. CONCLUSIONS: The prevalence of sib-pair diabetes is 3.64%. The second affected siblings were older. MODY is unlikely and Class I and II HLA genes was present in sib-pair diabetes.

The epidemiology, clinical, biochemical, immunological and radiological features of youth onset type 2 diabetes mellitus in the state of Qatar.

Objectives: To describe the epidemiology, clinical, biochemical, immunological and radiological aspects of youth with type 2 diabetes. Methods: Patients under 18 year of age with type 2 diabetes were recruited from 2018 to 2020, clinical data collected, autoantibodies (GAD65, IAA, IA2 and ZnT8), insulin, ALT and c-peptide were measured. Hepatic ultrasound was performed for assessment of non-alcoholic fatty liver disease (NAFLD). Results: 104 patients were identified. The incidence in 2020 and prevalence per 100,000 was 2.51 and 23.7, respectively. The age of onset was between 8.5 and 18 years with 74% of the patients being of Qatari nationality. Males were more affected than females (1.5/1). Overweight/obesity was present in 98% of all the patients, a positive family history (either both parents or a single parent) in 71% and maternal gestational diabetes mellitus (GDM) in 60% of patients. More than 90% of the patients had acanthosis nigricans. 5 patients had 1 autoantibody positivity and hepatic ultrasound detected evidence of NAFLD in majority of patients. Conclusion: Obesity, maternal GDM and family history of diabetes were the key risk factors for the development of type 2 diabetes. Autoantibody positivity may be present in youth type 2 diabetes. As youth type 2 diabetes is associated with early onset microvascular and macrovascular complications, these findings have important social and health budget implications for Qatar. Tackling the burden of maternal GDM and childhood obesity and building programmes for early detection and intervention, are therefore, essential to reduce the risk of future complications.

Growth, bone maturation and ovarian size in girls with early and fast puberty (EFP) and effects of three years treatment with GnRH analogue (GnRHa).

INTRODUCTION: Early puberty (EP) in girls is defined as the onset of thelarche that begins after 6 years and before 8 years and/or acceleration in the tempo of pubertal development. The stage of puberty and the ovarian volume at presentation and the effect of treatment with GnRH analogue (GnRHa) on final adult height are still debated. PATIENTS AND METHODS: We analyzed the data of 22 girls, who presented early and fast puberty (FEP). The clinical stage of puberty, hormonal levels and the ovarian volume (OV) (measured by ovarian ultra-sonography) at presentation were studied. We recorded the effects of 3 years treatment with GnRHa on their growth in relation to their mid parental height, pubertal progression, and bone maturation. RESULTS AND CONCLUSION: GnRHa therapy decreased the fast progress of puberty, skeletal maturation, and GV/year. It was successful in increasing the predicted final adult height comparable to or surpassing their mid-parenteral height. A larger OV at presentation was associated with reduced Ht-SDS after 3 years of GnRHa treatment. Clearly, a definitive evaluation of the efficacy of GnRHa as treatment for EFP in girls will require expanded and concerted studies.

Clinical and metabolic characteristics of children with hybrid diabetes mellitus (HD) compared to children with type 2 diabetes mellitus (T2DM): A preliminary comparative study.

BACKGROUND: The term double diabetes or "Hybrid Diabetes (HD)" describes diabetes with combined features of type 1 and type 2 diabetes (T2DM). PATIENTS AND METHODS: We report the clinical and biochemical characteristics of 7 children with HD and the course of their disease including the response to treatment. The data were compared to 59 children with a diagnosis of T2DM. Variables examined included age, height, weight, body mass index (BMI), triglycerides (Tg), high-density lipoprotein (HDL), and blood pressure. The Weiss criteria were used to diagnose metabolic syndrome (MetS). The atherogenic index of plasma (AIP) was calculated from the standard lipid profile. Four autoantibodies against pancreatic ß-cell were measured in all patients. RESULTS: Significant clinical and biochemical differences were detected among children with HD versus T2DM. The mean BMI of children with T2DM was significantly higher than for the HD group. At presentation, the mean C peptide level was significantly lower in HD versus T2DM group and 28% presented with diabetic ketoacidosis (DKA). The percentage of those with full criteria of MetS was significantly higher in T2DM versus HD group as well as the percentage of children with high atherogenic index. After a mean duration of 2.3 months from diagnosis, 4/7 of HD patients stopped insulin therapy and 3 patients had a marked reduction in the insulin requirement. During the follow-up (after 15 ±5 months), 5/7 HD patients required an increase in their insulin dose, one was controlled on a markedly low dose of basal insulin and the last patient did not require any insulin therapy for 40 months. CONCLUSION: Appropriate assessment of HD is necessary for early and correct diagnosis. Increasing awareness of HD among the general population and primary care practitioners is necessary for successfully and properly treating this complex disease.

Clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus among children in Qatar.

To describe the clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus (T1DM). Patients (0-18 years) with diabetes were recruited. Clinical data was collected, autoantibodies and c-peptide were measured. Whole Genome Sequencing was performed. Genomic data analysis was compared with the known genes linked with T1DM and HLA alleles were studied. 1096 patients had one or more antibody positivity. The incidence of T1DM in 2020 was 38.05 per 100,000 children and prevalence was 249.73. GADA was the most common autoantibody followed by IAA. Variants in GSTCD, SKAP2, SLC9B1, BANK1 were most prevalent. An association of HLA haplotypes DQA1*03:01:01G (OR = 2.46, p value = 0.011) and DQB1*03:02:01G (OR = 2.43, p value = 0.022) was identified. The incidence of T1DM in Qatar is the fourth highest in the world, IA2 autoantibody was the most specific with some patients only having ZnT8 or IA2 autoantibodies thus underlining the necessity of profiling all 4 autoantibodies. The genes associated with T1DM in the Arab population were different from those that are common in the Caucasian population. HLA-DQ was enriched in the Qatari patients suggesting that it can be considered a major risk factor at an early age.

Impact of oral nutritional supplements (ONS) on growth outcomes and IGF-1 level in underweight older children and young adolescents (5-14 years) with short stature and no systemic disease: High versus normal calories density formula.

OBJECTIVES: This controlled trial investigated the effects of energy-dense pediatric oral nutritional supplements ONS versus standard ONS in pediatric patients requiring oral nutritional support for low body mass index (BMI) or weight gain per day (WGD) below the average for age and sex.  Patients and Methods: 34 children and adolescents (mean age 10.2 years) with faltering growth requiring ONS were randomized to cONS (n =22) or sONS (n = 12) for a year. We recorded their weight (WT), height (HT) and calculated height growth velocity (GV), Ht-SDS, BMI, WGD, every 3 months for a year.  Results: The WGD, height growth velocity (GV: cm/year), and Ht-SDS increased significantly, in both groups, during the year of ONS. The use of the cONS resulted in significantly greater mean total WGD and BMI-SDS after 6 months and 1 year, compared to the sONS group. The increase in IGF1-SDS was significantly higher in the cONS groups versus the sONS group. Moreover, the WGD was correlated significantly with the height GV during the year of ONS intake. CONCLUSIONS: ONS improved the growth of underweight old children and adolescents who had no systemic illness. There was a significantly higher WGD and BMI-SDS in the group on cONS compared to those on sONS. In both groups, long-term use of ONS significantly improved Ht-SDS.

The prevalence, immune profile, and clinical characteristics of children with celiac disease and type 1 diabetes mellitus in the state of Qatar.

OBJECTIVES: Children with antibody positive type 1 diabetes mellitus (type 1 diabetes) are at an increased risk of developing celiac disease (CD) which suggests a common autoimmune basis with both high-risk human lymphocyte antigen (HLA) and non-HLA factors playing a role in the pathophysiology. We aim to describe the prevalence, immune profile, and clinical characteristics of children with CD who have type 1 diabetes mellitus in Qatar. METHODS: All children (aged 0-18 years) attending a regional diabetes clinic with antibody positive type 1 diabetes were screened for CD. Measurement of tissue transglutaminase IgA and IgG as well as anti-endomysial antibody, was done, clinical details about the birth history, family history of diabetes and CD, age of onset, and ethnicity were collected. RESULTS: Out of the 1,325 children with antibody positive type 1 diabetes, 54 were identified to have CD on screening and then confirmed on small bowel biopsy. The prevalence of CD in the type 1 diabetes childhood population in Qatar is 4.07%. CD and type 1 diabetes were more prevalent in the Qatari children (n=32) as compared to non-Qatari (n=22) and occurred mostly in the age group 6-10 years. The most common type 1 diabetes antibodies in children with CD were glutamic acid decarboxylase and insulin autoantibody. Twelve subjects were asymptomatic for CD symptoms and picked up only on screening. CONCLUSIONS: The prevalence of CD in children with type 1 diabetes in Qatar is comparable to reports from around the world. Many children were asymptomatic and thus routine screening is recommended.

The Epidemiology and Genetic Analysis of Children With Idiopathic Type 1 Diabetes in the State of Qatar.

CONTEXT: Idiopathic type 1 diabetes is characterized by the absence of autoantibodies and the underlying mechanisms are not clear. OBJECTIVE: We aimed to study the epidemiology, describe the clinical characteristics, and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes. METHODS: This was a prospective study of type 1 diabetes patients attending Sidra Medicine from 2018 to 2020. Autoantibodies (GAD65, IAA, IA-2A, and ZnT8) were measured and genetic testing was undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes were compared with patients with autoimmune type 1 diabetes. RESULTS: Of 1157 patients with type 1 diabetes, 63 were antibody-negative. Upon genome sequencing, 4 had maturity onset diabetes of the young (MODY), 2 had Wolfram syndrome, 1 had H syndrome, and 3 had variants of uncertain significance in MODY genes; 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10 to 14 years. C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average body mass index was in the normal range and 33% of the patients had a history of diabetic ketoacidosis (DKA). CONCLUSION: Four percent of the children had idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the 2 groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is unknown but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.

Growth response to growth hormone (GH) treatment in children with GH deficiency (GHD) and those with idiopathic short stature (ISS) based on their pretreatment insulin-like growth factor 1 (IGFI) levels and at diagnosis and IGFI increment on treatment.

OBJECTIVES: Some idiopathic short stature (ISS) patients may have varying degrees of insulin-like growth factor 1 (IGFI) deficiency. Others with growth hormone deficiency (GHD) (peak GH < 7 ng/dL after provocation) have normal IGFI levels. Do children with ISS or those with GHD with variable pretreatment IGFI standard deviation score (IGFISDS) have different IGFI and growth responses to recombinant human growth hormone (rhGH) therapy? METHODS: We studied the effect of GH therapy (0.035-0.06 mg/kg/day) on linear growth and weight gain per day (WGPD) in children with ISS (n=13) and those with GHD (n=10) who have low pretreatment IGFISDS (IGF SDS < -1.5) and compared them with age-matched prepubertal children with ISS (n=10) and GHD (n=17) who had normal pretreatment IGFISDS. An untreated group of children with ISS (n=12) served as a control group. RESULTS: At presentation, the height standard deviation score (HtSDS) of children with ISS who had low pretreatment IGFISDS was significantly lower compared to the normal IGFI group. The age, body mass index (BMI), BMISDS, peak GH response to clonidine provocation and bone age did not differ between the two study groups. After 1 year of treatment with rhGH (0.035-0.06 mg/kg/day) IGFISDS increased significantly in both groups (p<0.05). Both had significantly increased HtSDS (catch-up growth). The increase in the HtSDS and WGPD were significantly greater in the lower pretreatment IGFISDS group. The IGFSDS, BMISDS, HtSDS and difference between HtSDS and mid-parental HtSDS were significantly greater in the rhGH treated groups vs. the not treated group. In the GHD groups (normal and low IGFISDS), after 1 year of GH therapy (0.03-0.05 mg/kg/day), the HtSDS increased significantly in both, (p<0.01). The WGPD and increment in BMI were significantly greater in children who had low pretreatment IGFISDS. There was a significant increase in the IGFSDS in the two treated groups (p<0.05), however, the WGPD was greater in the pretreatment low IGFISDS. CONCLUSIONS: IGFI deficiency represents a low anabolic state. Correction of IGFI level (through rhGH and/or improved nutrition) in short children (ISS and GHD) was associated with increased linear growth and WGPD denoting significant effect on bone growth and muscle protein accretion.

Epidemiology, genetic landscape and classification of childhood diabetes mellitus in the State of Qatar.

AIMS/INTRODUCTION: To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar. MATERIALS AND METHODS: All patients (aged 0-18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated. RESULTS: Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000. CONCLUSIONS: This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non-Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus.

Corneal nerve loss in children with type 1 diabetes mellitus without retinopathy or microalbuminuria.

AIMS/INTRODUCTION: Corneal confocal microscopy is a rapid, non-invasive ophthalmic technique to identify subclinical neuropathy. The aim of this study was to quantify corneal nerve morphology in children with type 1 diabetes mellitus compared with age-matched healthy controls using corneal confocal microscopy. MATERIALS AND METHODS: A total of 20 participants with type 1 diabetes mellitus (age 14 ± 2 years, diabetes duration 4.08 ± 2.91 years, glycated hemoglobin 9.3 ± 2.1%) without retinopathy or microalbuminuria and 20 healthy controls were recruited from outpatient clinics. Corneal confocal microscopy was undertaken, and corneal nerve fiber density (n/mm2 ), corneal nerve branch density (n/mm2 ), corneal nerve fiber length (mm/mm2 ), corneal nerve fiber tortuosity and inferior whorl length (mm/mm2 ) were quantified manually. RESULTS: Corneal nerve fiber density (22.73 ± 8.84 vs 32.92 ± 8.59; P < 0.001), corneal nerve branch density (26.19 ± 14.64 vs 47.34 ± 20.01; P < 0.001), corneal nerve fiber length (13.26 ± 4.06 vs 19.52 ± 4.54; P < 0.001) and inferior whorl length (15.50 ± 5.48 vs 23.42 ± 3.94; P < 0.0001) were significantly lower, whereas corneal nerve fiber tortuosity (14.88 ± 5.28 vs 13.52 ± 3.01; P = 0.323) did not differ between children with type 1 diabetes mellitus and controls. Glycated hemoglobin correlated with corneal nerve fiber tortuosity (P < 0.006) and aspartate aminotransferase correlated with corneal nerve fiber density (P = 0.039), corneal nerve branch density (P = 0.003) and corneal nerve fiber length (P = 0.037). CONCLUSION: Corneal confocal microscopy identifies significant subclinical corneal nerve loss, especially in the inferior whorl of children with type 1 diabetes mellitus without retinopathy or microalbuminuria.

Long-term prednisone versus hydrocortisone treatment in children with classic Congenital Adrenal Hyperplasia (CAH) and a brief review of the literature.

BACKGROUND: Debate still exist about the safety of long-term use of prednisone (PD) versus hydrocortisone (HC) for treating children with congenital adrenal hyperplasia -21OH D (CAH). Despite recent developments in congenital adrenal hyperplasia -21OH D (CAH), several issues related to patient growth and final height remain unsolved. Debate still exist about the safety of long-term use of PD versus HC for treating children with CAH. The mechanism by which glucocorticoid therapy interferes with growth is complex and multifactorial. Relatively slight supra-physiologic levels may be enough to blunt growth velocity. An increased risk of developing obesity is another possible consequence of hyper-cortisolism in children with CAH. OBJECTIVES OF THE STUDY: To evaluate the anthropometric and biochemical effects of long-term PD versus HC treatment in children with CAH-21OHD. A brief review of the literature is also reported. PATIENTS AND METHODS: This retrospective study evaluated linear growth and biochemical data of thirty children with classic CAH (19 females and 11 males), who were on PD (n=22) or HC (n=8) treatment, since their first diagnosis. Clinical data included age, gender, duration of therapy, dose of HC and or equivalent dose of HC in the PD group, blood pressure, height (Ht) and weight. Ht-SDS and BMI were also calculated. Biochemical data included measurement of 17- OH progesterone, cholesterol, triglycerides (TG), HDL, LDL, fasting glucose, and insulin concentrations. HOMA-IR was calculated. Carotid intima-media thickness (CIMT) was measured using high-resolution B-mode ultrasonography. Thirty normal age matched children were used as controls for the anthropometric and CIMT data. RESULTS: The age of children and duration of treatment did not differ among the two treatment groups. After a mean of 6 years of treatment, the Ht-SDS and BMI did not differ between the three groups of children. The equivalent hydrocortisone dose of children on prednisone was significantly higher than the dose for the hydrocortisone group. Both systolic and diastolic blood pressures (BP) of children on PD was slightly higher compared to those on hydrocortisone group. However, the BP of the 2 treatment groups was not different compared to control children. Fasting blood glucose, homeostatic model assessment insulin resistance (HOMA-IR), plasma TG, HDL, and cholesterol did not differ among the two treatment groups. LDL levels were significantly higher in the PD group versus the HC group. The mean CIMT did not differ among the two treatment groups but was significantly higher in the treated groups versus controls. There was a significant linear correlation between BMI-SDS and CIMT (r=0.37, p=0.047). CONCLUSIONS: Children with CAH-21OHD who were kept on PD therapy for 6.4±2.7 years, since the beginning of diagnosis, have maintained normal linear growth. No difference in BMI, HOMA-IR, or CIMT was detected among the two treated groups. The efficiency, safety and convenience of a single daily dose of PD could be a good and relatively safe alternative to HC for the continuing medical treatment of patients with CAH-21OHD. However, more prospective studies across childhood and adolescence are necessary to draw definitive conclusions.

Postnatal growth of Infants with neonatal diabetes: insulin pump (CSII) versus Multiple Daily Injection (MDI) therapy.

BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life. Their diabetes is associated with partial or complete insulin deficiency with variable degree of intrauterine growth retardation. Insulin therapy corrects the hyperglycemia and results in improvement of growth. However, no studies have reported the longitudinal growth of these infants (head circumference, length and weight gain) after starting insulin therapy. PATIENTS AND METHODS: We assessed the growth parameters weight (Wt), Length (L) and head circumference (HC) in 9 infants with PNDM, during the first 2 years of their postnatal life. Five infants were on insulin pump therapy (CSII) and 4 were on multiple doses of insulin injection (MDI) therapy. RESULTS: On insulin therapy for 20±4 months catch-up growth occurred in the majority of infants. L-SDS increased from -1.45 to -0.65 , HC-SDS from -2.3 to - 0.51 and Wt-SDS increased from -1.94 to - 0.7 at the end of the 20±4 months of age, after starting insulin therapy. Two out of 9 infants had a L-SDS <-2 , in 4 Wt-SDS was <-2 and in 1 the HC-SDS was <-2 at  at 20±4 months of postnatal growth.  The level of HbA1c was lower in infants on CSII compared to those on MDI (9.6±1%) compared to those on MDI (10.2±2%). However, growth parameters improved significantly in both groups (CSII and MDI) with no significant difference among them. CONCLUSIONS: Infants with PNDM with positive anti-GAD and antiTPO were diagnosed later and their intra-uterine and postnatal growth differed compared to those with negative antibodies. The majority of infants with PNDM exhibited significant catch up growth within the first two years of life irrespective of the etiology of diabetes. HbA1c appeared to be better in infants with PNDM on CSII therapy when compared to those on MDI therapy.

Responses to growth hormone (GH) therapy in short children with normal GH secretion and no bone age delay: an analysis of potential factors affecting their response to rhGH therapy. A controlled study.

BACKGROUND: Variability still exist about the growth response to growth hormone (GH) therapy in children with idiopathic short stature (ISS). We describe the growth response to rhGH therapy for >2 years in 20 prepubertal children with idiopathic short stature (ISS) and 18 children with GH deficiency (GHD) and compared them with 15 children with ISS who did not receive rhGH therapy. PATIENTS AND METHODS: Our study included 35 prepubertal and peripubertal (Tanner 1 and 2) children with short stature (Ht-SDS <-2) and/or Ht-SDS >1SD below their mid parental height SD (MP-Ht-SDS) with slow growth velocity (<-1 SD), with normal peak GH response to provocation tests (15.5±6.5 ng/dl), normal IGF-I SDS (-0.9±0.6), and no bone age delay (± 1 year from chronological age) (ISS). 20 children were treated for 2.5±1.5 years with rhGH 0.05 mg/kg/day and 15 children were not treated with rhGH. 18 children with diagnosis of GHD, diagnosed in the same period, receiving rhGH therapy served as controls. We assessed the linear growth and IGF-I levels of all children for an average of 2 years. RESULTS: Children with ISS on rhGH therapy had a height gain of 0.77 SD in 2 years versus 1.05 SD in GHD children, with significant increase in IGF-I and normal progression of bone age and puberty. Children with ISS who did not receive rhGH had no gain in the changes of Ht-SDS inspite of normal progression of bone age and puberty. The difference between children Ht-SDS and mid-parental height SDS (MP-Ht-SDS) changed significantly from -1.1±3 to -0.3±0.5 in the ISS group and from -1.35±0.5 to -0.3±0.25 in the GHD group, after an average of 2 years of treatment. In the treated ISS group, the Ht-SDS gain was correlated positively with the duration of rhGH therapy (r = 0.82, p<0.0001), negatively with the age at the start of treatment (r = -0.544, p = 0.01), and positively with the bone age (r =-0.44, p = 0.04). DISCUSSION: The Ht-SDS of children with ISS on rhGH treatment closely approached their MP-Ht-SDS after 2 years of rhGH therapy while those who did not receive rhGH kept the same distance from their MP-Ht-SDS after 2 years. Analysis of possible factors affecting linear growth in children with ISS on rhGH therapy showed that children below 9 years with Ht-SDS <-2.5 SD and those with Ht-SDS >1SD below MP-Ht-SDS grew better on rhGH therapy compared to older children and those with Ht-SDS >-2.5 and were less than 1SD from their MP-HT-SD. Higher doses of rhGH (to keep IGF-I in high normal levels) and longer duration of therapy improved the Ht-SDS gain of these children. CONCLUSION: We report significant gain in Ht-SDS in prepubertal children with ISS on rhGH therapy and better response in younger children and in those with Ht-SDS > 1 SD below their MP-Ht-SDS.

Linear growth in relation to the circulating concentration of insulin-like growth factor-I in young children with acyanotic congenital heart disease with left to right shunts before versus after surgical intervention.

OBJECTIVES: The aim was to determine the degree of linear growth retardation of patients with congenital acyanotic heart disease at presentation and the magnitude of catch-up growth, if any, in relation to their echocardiographic changes and insulin-like growth factor- I (IGF-I) concentration before versus after surgical intervention. MATERIALS AND METHODS: This prospective study recorded the anthropometric data and measured the circulating IGF-I, free thyroxin (FT4), and thyrotropin (TSH) of 27 infants and children with congenital acyanotic heart disease with left to right shunt (10 with VSD, 8 with ASD, 9 PDA) without heart failure, or severe pulmonary hypertension, before and 12 months or more after surgical or catheter intervention. Eighty normal age and sex- matched normal siblings of these patients were included as controls for the auxologic data. RESULTS: At presentation, patients' mean age = 35.6 ± 26 months, height SDS (HtSDS) = -1.6 ± 1.1, and body mass index (BMI) = 15.1 ± 2.5. They were significantly shorter and with lower BMI compared to normal controls (HtSDS = 0.25 ± 0.3, BMI = 16.4 ± 1.5). One year or more after catheter or surgical treatment, the HtSDS and BMI increased significantly in patients to -0.55 ± 0.9 and 15.9 ± 1.5, respectively). IGF-I levels increased from 46.8 ± 29 mcg/L before to 77.3 ± 47.6 mcg/L after intervention. No significant change has been detected in circulating FT4 or TSH concentrations. The HtSDS after treatment was correlated with the IGF-I concentration (r = 0.804, P < 0.001). The change in the HtSDS after intervention was correlated significantly with BMI (r = 0.594, P 0.001) and negatively with age (r = -0.52, P< 0.01). The shunt size was correlated negatively with BMI and HtSDS before intervention (r = -0.35, P < 0.01 and 0.01 and r = -0.461, P < 0.05, respectively). GVSDS after intervention surgery was correlated with BMI after intervention (r = 0.495, P < 0.001) and negatively with the age at operation (r = -0.683, P < 0.001). CONCLUSIONS: In congenital acyanotic heart diseases, early surgical interference and weight gain have beneficial effect on postoperative growth spurt. This catch-up growth appears to be mediated through activation of the GH/IGF-I system and suggests an important role of increasing BMI (an indicator of nutrition) as an imperative factor.

Linear growth and neurodevelopmental outcome of children with congenital hypothyroidism detected by neonatal screening: A controlled study.

INTRODUCTION: Different growth and neuro-developmental outcomes have been associated with different doses of thyroxine given to infants with congenital hypothyroidism (CH). MATERIALS AND METHODS: We studied the longitudinal growth pattern and assessed the neurodevelopment of 45 children with CH(25 girls, 20 boys) diagnosed through the national screening program in Qatar, for 6 years or more to examine the effects of initial T4 dosage (50 µg/day) with adjustment of T4 dose to maintain serum free T4 concentrations within the upper quartile of normal range and thyroid stimulating hormone < 4 mIU/mLThe birth size of newborns with CH diagnosed through the screening program before January 2003, was recorded and their growth in weight and stature was monitored every 3 months for at least 6 years of life. The IQ of children was assessed between 3 and 6 years of age using The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). RESULTS: Birth weight, length, and head circumference of patients (3.21 ± 0.43 kg, 50.5 ± 3.21 cm and 34.1 ± 1.5 cm, respectively) did not differ than those for 10,560 normal newborns with normal thyroid function (3.19 ± 0.59 kg, 50.5 ± 2.2 cm and 34.2 ± 1.7 cm). During the first year CH children growth (25.8 ± 2.8 cm/year) was similar to those for normal infants (25.5 ± 0.75 cm/year). During the first 6 years, stature growth was normal in all children with CH versus Center for disease control and prevention (CDC) data. The mean height standard deviation score (HtSDS) of children with CH showed adjustment (± 0.5 SD) toward their mid-parental height SDS (MPHtSDS) only during the second year of life. The children's mean HtSDS was higher by an average of 0.4 SD between the 2(nd) and 7(th) year of life. CONCLUSION: These data proved that effective screening and treatment completely assures normal neurodevelopment and linear growth in patients with CH. The data showed that their HtSDS slightly exceeds their MPHtSDS during childhood.

The effect of vitamin D therapy on hematological indices in children with vitamin D deficiency.

We investigated the effect of vitamin D on hematological indices, blood pressure (BP) and heart rate (HR) in children with vitamin D deficiency before and after treatment. Vitamin D deficiency does not have a significant effect on red blood cell count and indices, total and differential white blood cell count, or on BP and HR. A mega-dose vitamin D therapy did not have a significant effect on all these parameters in children.

Linear growth and circulating insulin-like growth factor I in children with tufting enteropathy receiving long-term TPN.

We analyzed the growth of 12 children with tufting enteropathy for 2 years receiving total parenteral nutrition (TPN). At diagnosis, the length standard deviation score (SDS) (-2.15 ± 1.8) and body mass index (BMI) (12.6 ± 3.9) were significantly decreased. The height SDS and BMI of patients increased significantly (-1.39 ± 1.5 and 16.2 ± 1.9, respectively) after TPN. Partial catch-up growth was achieved in 7 of 12 children during the 2-year period, whereas linear growth velocity was maintained in an additional 3 patients. Insulin-like growth factor I levels correlated significantly with albumin and hemoglobin concentrations (P < 0.001), and increments in insulin-like growth factor I concentration after TPN were correlated with the changes in the BMI and height SDS (P < 001).