Vitamin D Intake and Status of Children With Sickle Cell Disease in Montreal, Canada.

Sickle cell disease (SCD) and vitamin D deficiency share manifestations such as bone complications and bony pains. Canadian SCD children are characterized by compromised sun exposure all year long and potential dietary deficiency, which combined to SCD-causing high nutritional demands, may lead to impaired vitamin D status. The objectives of this study were to document vitamin D status and intake and assess the relationship between vitamin D status and SCD-related outcomes in Canadian children with SCD followed in a tertiary pediatric center. Our study population included 119 children (47% males, median age [interquartile range]: 11.1 [9.2-14.8]) mainly of Haitian and Sub-Saharan African origin who had at least one measure of serum 25-hydroxyvitamin D (25OHD) performed between June 2015 and February 2017. Predominant genotypes were homozygous hemoglobin S (60%) and sickle hemoglobin-C (32%). Vitamin D deficiency (25OHD<30 nmol/L) and insufficiency (30 to 49 nmol/L) were present in 31% and 37% of children, respectively. Vitamin D-sufficient children (25OHD>50 nmol/L) had higher hemoglobin levels, lower leukocyte, reticulocyte, and neutrophil counts, compared with vitamin D-deficient and insufficient children. Vitamin D intake was low and modestly correlated to serum 25OHD levels. Acute SCD complications in the preceding 2 years were not associated with vitamin D status in these children.

Decreased regional left ventricular myocardial strain in type 1 diabetic children: a first sign of diabetic cardiomyopathy?

BACKGROUND AND OBJECTIVES: Type 1 diabetes is a major cardiovascular risk factor associated with an excess of mortality in young adults due to premature cardiovascular events, which includes heart failure. The relation between type 1 diabetes and cardiac structure and function in children was poorly documented. Our study investigates (1) whether type 1 diabetic children have echocardiographic signs of subclinical cardiac dysfunction assessed by tissue Doppler strain and (2) whether state of metabolic control and diabetes duration have any influence on the cardiac event. METHODS: Standard echocardiography and tissue Doppler imaging were prospectively performed in type 1 diabetic children. Left ventricular dimensions, standard indices of systolic and diastolic function, and septal longitudinal strain were investigated. RESULTS: Thirty consecutive asymptomatic diabetic children (age: 12.4 [5-17] years; males: 53%) were compared to 30 age and sex-matched healthy control subjects. Left ventricular mass index and diastolic septal thickness were significantly increased in diabetic children. There was no difference between two groups as regards the left ventricular ejection fraction and conventional mitral Doppler parameters (E, A, Ea). The global longitudinal systolic strain and strain rate were found to be decreased in children with diabetes. The global longitudinal early diastolic strain rate (Esr) was negatively correlated with metabolic control. Longitudinal strain was not correlated with diabetes duration. CONCLUSION: Children with Type 1 diabetes had subclinical alterations in left ventricular size and longitudinal myocardial deformation.

Adrenocortical tumor with precocious puberty in a 2-month-old girl.

Adrenocortical tumor is a rare childhood tumor with a median age at onset of 3.2 years. Virilization is the most common sign. Laparotomy is the reference treatment and has a favorable course. The diagnosis of adrenal tumor can be difficult. The main parameters of malignant tumors are size and metastasis. Analysis of TP53 mutation can facilitate final diagnosis. We report a case of virilizing adrenal tumor that developed in a 2-month-old girl, and which was treated with laparoscopic adrenalectomy.

The first familial case of inherited 2q37.3 interstitial deletion with isolated skeletal abnormalities including brachydactyly type E and short stature.

Albright hereditary osteodystrophy (AHO)-like syndrome is also known as brachydactyly-mental retardation syndrome (BDMR; OMIM 60040). This disorder includes intellectual disability in all patients, skeletal abnormalities, including brachydactyly E (BDE) in approximately half, obesity, and facial dysmorphism. Patients with 2q37 microdeletion or HDAC4 mutation are defined as having an AHO-like phenotype with normal stimulatory G (Gs) function. HDAC4 is involved in neurological, cardiac, and skeletal function. This paper reports the first familial case of 2q37.3 interstitial deletion affecting two genes, HDAC4 and TWIST2. Patients presented with BDE and short stature without intellectual disability, showing that haploinsufficiency of the HDAC4 critical region may lead to a spectrum of phenotypes, ranging from isolated brachydactyly type E to BDMR.

Alterations of left ventricular myocardial strain in obese children.

AIMS: Obesity may have implications in the myocardial structural change, which may contribute to mechanical consequences. Using 2D speckle echocardiography, we looked for myocardial changes and investigated their relation to obesity, inflammation, insulin resistance and physical capacity in children with isolated obesity. METHODS AND RESULTS: Standard echocardiography and 2D strain were prospectively performed in obese children and compared them with age- and sex-matched controls. Z-score body mass index (BMI Z-score), ultra-sensitive C reactive protein, indices of insulin resistance (HOMA-IR) and metabolic stress test were assessed in obese children. Thirty-two consecutive obese patients [age: 12.8 (8-17) years; 15 males; BMI Z-score: 5.8 [2.05-8.6)] were compared with 32 controls. Longitudinal strain and circumferential strain were significantly lower in the obese group (respectively -18.0 ± 2.4% vs. -20.6 ± 2.5%; P = 0.0001 and -18.2 ± 3.5% vs. -20.1 ± 2.3%; P = 0.013), while radial strain did not differ. Longitudinal strain was correlated with HOMA-IR (Pearson's rho = -0.39) and with the exercise capacity (Pearson's rho = 0.62). In the multivariate analysis, after adjusting for age, the mean arterial pressure and left ventricular (LV) mass, the BMI Z-score remained independently related to the longitudinal and circumferential strain. CONCLUSION: Childhood obesity may be associated with an early alteration of the longitudinal and circumferential LV strain. These findings have potentially significant clinical implications for the outcomes and follow-up of obese children meriting further studies.

Myocardial strain assessment in cystic fibrosis.

BACKGROUND: The aim of this work was to evaluate myocardial strain analysis as a tool for the early detection of left ventricular functional changes in patients with cystic fibrosis. METHODS: A total of 42 consecutive patients (mean age, 24 ± 7.5 years; 52% men) diagnosed with cystic fibrosis and referred for echocardiographic cardiac function assessment were prospectively enrolled. A group of healthy age-matched and gender-matched volunteers (n = 42) formed the reference population for echocardiographic comparisons. RESULTS: Left ventricular ejection fraction was conserved in both groups but was significantly lower in the cystic fibrosis group. Cardiac function assessment using Doppler tissue imaging parameters revealed that both systolic and diastolic measurements differed between the two groups: mitral peak systolic and diastolic velocities, as well as septal and lateral wall strain rates, were decreased in patients with cystic fibrosis, as was longitudinal strain of both the septal and lateral walls. CONCLUSIONS: Using strain measurements, subclinical changes in left ventricular function were found in patients with cystic fibrosis. These parameters were correlated with the degree of pulmonary involvement severity. These findings have potentially significant clinical implications for the outcomes and follow-up of patients with cystic fibrosis, meriting further studies.

Experience with intraamniotic thyroxine treatment in nonimmune fetal goitrous hypothyroidism in 12 cases.

CONTEXT: Nonimmune fetal goitrous hypothyroidism is a rare condition that can induce obstetrical and/or neonatal complications and neurodevelopmental impairments such as those still seen in some patients with congenital hypothyroidism. Prenatal treatment to prevent these adverse outcomes is appealing, but experience is limited and the risk to benefit ratio controversial. OBJECTIVE: The objective of the study was to evaluate the feasibility, safety, and effectiveness of intrauterine l-thyroxine treatment in a large cohort with nonimmune fetal goitrous hypothyroidism. DESIGN: This was a retrospective study of 12 prenatally treated fetuses diagnosed between 1991 and 2005 in France. METHODS: During pregnancy, goiter size and thyroid hormone levels were compared before and after prenatal treatment. At birth, clinical, laboratory, and ultrasound data were evaluated. RESULTS: Prenatal treatment varied widely in terms of l-thyroxine dosage (200-800 microg/injection), number of injections (one to six), and frequency (every 1-4 wk). No adverse events were recorded. During pregnancy, thyroid size decreased in eight of nine cases and amniotic-fluid TSH levels decreased in the six investigated cases, returning to normal in four. However, at birth, all babies had hypothyroidism, indicating that intraamniotic TSH levels did not reliably reflect fetal thyroid function. CONCLUSION: Our data confirm the feasibility and safety of intraamniotic l-thyroxine treatment for nonimmune fetal goitrous hypothyroidism. Although goiter size reduction is usually obtained, thyroid hormone status remains deficient at birth. Amniocentesis seems inadequate for monitoring fetal thyroid function. Further studies are needed to determine the optimal management of this disorder.

Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis.

OBJECTIVES: To describe the history, mechanisms, and consequences of cystic fibrosis (CF)-related diabetes, from childhood to early adulthood. STUDY DESIGN: Pancreatic beta-cell function was estimated from the plasma insulin/glucose ratios during oral glucose tolerance test (total area under the curve and deltaI(30-0min)/G(30min), homeostasis model assessment [HOMA]%B), insulin sensitivity with the HOMA%S index, in 237 children with CF (109 boys, 128 girls). Progression of glucose metabolism abnormalities was evaluated by analysis for interval censored data; rates of pulmonary transplantation and death by Kaplan-Meier analysis. RESULTS: Impaired glucose tolerance was found in 20% of patients at 10 years, 50% at 15 years, 75% at 20 years, 82% at 30 years; for diabetes, >20% at 15 year, 45% at 20 years, 70% at 30 years; for insulin treatment, 30% at 20 years, 40% at 30 years. Early impairment was associated with lower survival rates and higher rates of lung transplantation. The area under the curve(glucose) correlated with decreased body mass index and height. Decrease in early insulin secretion (deltaI(30-0min)/G(30min)) was associated with impaired glucose tolerance, in all estimates of insulin secretion with diabetes. HOMA%S did not differ between the groups. Increased inflammation correlated with insulin resistance and impaired glucose tolerance. CONCLUSIONS: CF-related diabetes, mainly because of beta-cell deficiency, is frequent early in life and associated with impaired nutritional state and growth, increased rates of terminal respiratory failure, and death.