The Hepcidin and 25-OH-Vitamin D Levels in Obese Children as a Potential Mediator of the Iron Status.

BACKGROUND: Obesity is associated with the risk factors such as iron and vitamin D deficiencies. Increased risk of iron deficiency generally correlates with the high levels of serum hepcidin in obese children. Vitamin D deficiency was also linked to an increase in serum hepcidin levels. We aimed to compare iron parameters and investigate the hepcidin levels in obese and non-obese children. METHODS: This study included 83 children and adolescents including obese (n = 35) and non-obese (n = 48). Laboratory values including serum iron levels, total iron-binding capacity, percentage of transferrin saturation, ferritin, reticulocyte parameters and high sensitivity C-reactive protein (hsCRP), hepcidin, 25-OH-Vitamin D were measured. RESULTS: Average levels of hepcidin, hsCRP, and ferritin were found to be similar in both study groups. Serum iron levels, total iron-binding capacity, percentage of transferrin saturation, and 25-OH-vitamin D levels were significantly lower in the obese group. There was no statistically significant difference between hepcidin and 25-OH-vi-tamin D levels. Average hepcidin levels were detected to be similar in both groups (p = 0.580) whereas, 25-OH-vi-tamin D levels were significantly lower in the obese group (p < 0.001). A statistically negative correlation was observed between average BMI (body mass index) and serum iron level (r = -0.476; p < 0.001), BMI and transferring saturation (r = -0.467; p < 0.001), and BMI and 25-OH-vitamin D levels (r = -0.474; p < 0.001). Hence, no statistically significant relation was detected between hepcidin and 25-OH-vitamin D levels (r = 0.233; p = 0.084). Being female, vitamin D deficiency, and IRF (%) (Immature Reticulocyte Fraction) were found as independent risk factors for BMI increase due to logistic regression analyses. CONCLUSIONS: In conclusion, observed statistical associations and correlations do not prove a causal relationship between the hepcidin levels and iron deficiency but vitamin D deficiency seems likely to cause high BMI levels or in contrast, obesity may cause vitamin D deficiency in the children. No association was found between hepcidin, ferritin, and hsCRP levels with obesity in children. However, vitamin D deficiency was detected to cause a 5.3-fold increase in BMI levels. We suggest that there may be different mechanisms in obesity-related metabolic and hematological events. One can also envision that there is not enough time for the chronic inflammation processes to develop during childhood as opposed to those frequently seen in adult obese individuals.

Fatal Pulmonary Embolism Due to Inherited Thrombophilia Factors in a Child With Wolfram Syndrome.

Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus (DM), optic atrophy, diabetes insipidus, and deafness. Poorly controlled type 1 DM increases the risk for thrombosis. However, coexistence of DM and hereditary thrombosis factors is rarely observed. Here we present the case of a 13.5-year-old, nonfollowed girl newly diagnosed with poorly controlled Wolfram syndrome on the basis of the results of clinical and laboratory examinations. On the eighth day after diabetic ketoacidosis treatment, pulmonary embolism developed in the subject. Thrombus identified in the right atrium using echocardiography was treated by emergency thrombectomy. Homozygous mutation in the methylenetetrahydrofolate reductase gene C677T, heterozygous factor-V Leiden mutation, and active protein C resistance were identified in the patient. The patient was lost because of a recurring episode of pulmonary embolism on the 86th day of hospitalization. We present this case to highlight the need for investigating hereditary thrombosis risk factors in diabetic patients in whom thromboembolism develops.

Interdisiplinary and intraobserver reliability of the Greulich-Pyle method among Turkish children.

OBJECTIVES: Greulich-Pyle (GP) is one of the most used method for bone age determination (BAD) in various orthopedic, pediatric, radiological, and forensic situations. We aimed to investigate the inter- and intra-observer reliability of the GP method between the most relevant disciplines and its applicability to the Turkish population. METHODS: One-hundred and eighty (90 boys, 90 girls) patients with a chronological age younger than 18 (mean 9.33) were included. X-rays mixed by the blinded investigator were evaluated by two orthopedists, two radiologists, and two pediatric endocrinologists to determine skeletal age according to the GP atlas. A month later the process was repeated. As a statistical method, Paired t-test was used for comparison, an Intraclass Correlation Coefficients test was used for reliability and a 95 % confidence interval was determined. Results were classified according to Landis-Koch. RESULTS: All results were consistent with chronological age (p<0.001), according to the investigators' evaluations compared with chronological age. At the initial evaluation, the interobserver reliability of the method was 0.999 (excellent); at the second evaluation, the interobserver reliability was 0.997 (excellent). The intra-observer reliability of the method was 'excellent' in all observers. When results were separately evaluated by gender, excellent intraobserver correlation and excellent correlation with chronological age were found among all researchers (>0.9). When X-rays were divided into three groups based on age ranges and evaluated, 'moderate' and 'good' correlations with chronological age were obtained during the peripubertal period. CONCLUSIONS: The GP method used in skeletal age determination has excellent inter- and intra-observer reliability. During the peripubertal period, potential discrepancies in bone age assessments should be kept in mind. This method can be used safely and reproducibly by the relevant specialists.

Variability in the age at diagnosis of diabetes in two unrelated patients with a homozygous glucokinase gene mutation.

Homozygous mutations in the glucokinase gene (GCK) result in a complete deficiency of the GCK enzyme, which leads to permanent neonatal diabetes mellitus. Whilst there has been one report of a patient (with a homozygous p.T168A) who was diagnosed with diabetes at the age of 2 months, all other cases were diagnosed with diabetes within the first 2 weeks of life. We now report a second unrelated patient with the same p.T168A GCK mutation who was diagnosed with diabetes at the age of 9 months. We conclude that the specific GCK mutation, as yet unidentified genetic modifiers, and/or environmental factors might have different effects on pancreatic beta-cell functions, causing variability in the age at diagnosis of diabetes.

One-year follow-up of penis and testis sizes of healthy Turkish male newborns.

Penile length, penile diameter and testicular volume at birth reflect the activity and normality of the hypothalamus-pituitary-testicular axis. In this prospective longitudinal study, we aimed to measure penis and testicular size in healthy newborns at birth and 6 and 12 months of age. Seven hundred forty-six term healthy male newborns were enrolled in the study. According to measurements taken within 48 hours after birth, mean penile length (MPL) was 2.81 +/- 0.32 cm, mean penile diameter (MPD) 1.04 +/- 0.09 cm, right testicular volume (TV) 1.73 +/- 0.45 ml, and left TV 1.64 +/- 0.48 ml. At 6 months of age, MPL was 3.67 +/- 0.35 cm, MPD 1.23 +/- 0.08 cm, right TV 2.07 +/- 0.31 ml, and left TV 2.00 +/- 0.27 ml. At 12 months of age, MPL was 4.47 +/- 0.43 cm, MPD 1.25 +/- 0.09 cm, right TV 2.01 +/- 0.12 ml, and left TV 2.01 +/- 0.13 ml. There was a weak albeit statistically significant correlation between weight, length and PL at birth. In conclusion, the MPL of newborns was shorter than that reported in the published data from other populations. This situation may be related to ethnicity in addition to the lower birth weight and length of our subjects when compared to the newborns in other populations. We observed a significant increase, more marked during the first six months, in MPL, MPD and TV, which can be explained by the hormonal mechanism during minipuberty.

Rapid molecular diagnosis of ALB gene variants prevents unnecessary interventions in familial dysalbuminemic hyperthyroxinemia.

OBJECTIVES: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition caused by heterozygous gain-of-function mutations in the human ALB gene. CASE PRESENTATION: We report, a three-year-old boy with FDH due to p.R242P (or p.R218P without signal peptide) mutation in the ALB gene with a phenotype characterized by extremely high serum total and free thyroxine concentrations. His parents had normal thyroid function tests (TFT), so the mutation detected in this patient is assumed "de novo". Although the most frequent variant was p.R242H in Caucasians and p.R242P in Japanese, our patient had p.R242P variant. CONCLUSIONS: Early identification of FDH is fundamental to prevent unnecessary repeats of TFT with different methods. We encourage the ALB gene hot spot sequencing initially and indicate that this molecular diagnosis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.

Neonatal Problems and Infancy Growth of Term SGA Infants: Does "SGA" Definition Need to Be Re-evaluated?

Introduction: The exact definition of small-for-gestational-age (SGA) infant is still controversial among clinicians. In this study, we aimed to understand which definition is better in terms of establishing both early postnatal problems and growth. In this way, we compared early neonatal problems and infancy growth of term infants with birth weight (BW) < -2 SDS and with BW between 10th percentile (-1.28 SDS) and -2 SDS. Methods: A single center retrospective cohort study was conducted. Preterm infants, multiple gestations and newborns with any congenital anomalies were excluded from the study. Study group was defined as Group 1 (n = 37), infants BW < -2.00 SDS; Group 2 (n = 129), between -1.28 and -2.00 SDS; and Group 3 (n = 137), randomly selected newborns with optimal-for-gestational-age (BW between -0.67 and +0.67 SDS) as a control group. Results: The incidence of severe hypoglycemia was highest in Group 1 (%10.8) and Group 2 and 3 had similar rates of severe hypoglycemia (0.8 and 0.7%, respectively). The incidence of polycythemia was 5.4% in Group 1 and was significantly higher than Group 3 (0.0%) while it was 2.3% in Group 2. Short stature (length < -2 SDS) ratio at the age of 1 and 2 years were similar in each group. Overweight/obesity ratio at the age of 1 were 9.5, 20.8 and 16.7% in each group, respectively (p = 0.509). Conclusion: This study was planned as a pilot study to determine potential differences in the problems of hypoglycemia, polycythemia, and growth according to the differences in definition. Short term disturbances such as hypoglycemia and polycythemia are found to be higher in infants with a BW SDS below -2. From this point of view, of course, it will not be possible to change the routine applications immediately, however this study will be an initiative for discussions by making long-term studies.

Cranial MRI Abnormalities and Long-term Follow-up of the Lesions in 770 Girls With Central Precocious Puberty.

CONTEXT: Central precocious puberty (CPP) may arise from central nervous system (CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year olds, in whom the necessity of magnetic resonance imaging (MRI) is debated. OBJECTIVE: To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP. METHODS: A multicenter cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005 and 2017. Age at puberty onset was <6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2 ± 3.1 years). Potential predictors of CNS lesions were evaluated by univariate analyses. RESULTS: A total of 104/770 (13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly, related and 3.8% were incidental. Only 2 (0.25%) neoplastic lesions (1 low grade glioma and 1 meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast development <6 years (odds ratio [OR] 2.38; 95% CI 1.08-5.21) and the peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio >0.6 (OR 3.13; 95% CI 1.02-9.68) were significantly associated with CNS lesions. However, both patients with neoplastic lesions were >6 years old. CONCLUSION: Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.

Gonadal dysfunction and pelvic sonographic findings in females with thalassaemia major.

OBJECTIVE: To investigate pubertal and menstrual problems and evaluate pelvic sonographic findings in patients with beta-thalassaemia major. MATERIAL AND METHODS: Twenty-five female patients followed for thalassaemia major constituted the study population. Sexual maturation and hormonal status were assessed. Pubertal and menstrual problems were investigated. RESULTS: There was one patient with delayed puberty and five patients with arrested puberty. Mean ferritin level in this group of patients was slightly but not significantly higher than patients with normal pubertal maturation (2620 +/- 994 ng/ml vs. 2409 +/- 1348 ng/ml, p > 0.05). There were 10 patients with primary amenorrhoea, three with secondary amenorrhoea, five with oligomenorrhoea and irregular menstruation and one with regular menstruation. Compared to menstruating patients, the mean uterine size was smaller (4.1 +/- 3.5 cm(3) vs. 52.8 +/- 14.5 cm(3)) in all patients with delayed and arrested puberty (p < 0.05). Ten patients were taking hormone replacement therapy (HRT). The mean uterine size in these patients was larger than that in patients with amenorrhoea who were not taking HRT, but smaller than that in menstruating patients (9.1 +/- 15.9 cm(3), 2.7 +/- 1.3 cm(3) and 52.8 +/- 14.5 cm(3), respectively) (p < 0.05). CONCLUSION: Thalassaemia major has important side effects on the hypothaloma-pituitary-gonadal axis resulting in pubertal and menstrual abnormalities. HRT should be given to provide normal sexual maturation in these patients.

Factors affecting onset of puberty in Denizli province in Turkey.

The relationship between the possible factors affecting pubertal onset and pubertal timing was investigated in the Denizli province in Turkey. A total number of 3311 subjects (1562 girls, 1749 boys) aged 6-16.5 years participated in this study. Body mass index (BMI) was calculated. Pubertal stages were assessed according to methods of Marshall and Tanner. Testicular volume was determined using Prader orchidometer. Menarcheal age was recorded. All parents and students completed different questionnaires on demographic variables affecting pubertal timing such as socioeconomic conditions, psychosocial factors, exercise, nutritional status, chronic diseases, migration and birth weight. Using distribution percentiles of pubertal stages according to age, the relation between pubertal timing and factors affecting puberty was investigated. There was no significant association between exercise, birth weight, migration, chronic disease, and socioeconomic status and age of puberty onset. Menarcheal age of overweight and obese girls was significantly lower than that of girls with normal weight. In-family stress was the cause of early puberty in girls and of delayed puberty in boys.

Attention-deficit Hyperactivity Disorder Symptoms and Conduct Problems in Children and Adolescents with Obesity.

OBJECTIVES: Recent studies focus on the potential factors that increase the potantial risks of obesity in children and adolescents. According to research for the past years, one of the factors that increases the risk of obesity may be attention- deficit hyperactivity disorder (ADHD). We hypothesized that overweight/obese children and adolescents that apply to pediatric endocrinology for treatment would be at higher risk for ADHD symptoms. METHODS: In this cross-sectional study, the sample consisted of 55 children and adolescents aged between 6-14 years with body mass index greater than 95th percentile and 37 nonobese control group. Sociodemographic form, Strengths and Difficulties Questionnaire and The Turgay Diagnostic and Statistical Manuel of Mental Disorders Based Child and Adolescent Behavior Disorders Screening and Rating Scale has been used. RESULTS: The rates of inattentive subtype, hyperactivity/impulsivity subtype, and the combined type in the subject group were 10.9%, 3.6% and 7.3%, respectively. The rates of inattentive subtype, hyperactivity/impulsivity subtype were 5.4%, 2.7%, respectively, in the nonobese group. In terms of SDQ scores, peer problems subscale scores were significantly higher in the subject group than the control group (5.13±1.24 vs 4.32±1.18, p=0.003). According to the binary regression analysis, having peer problems was found to be significantly related to being obese (Exp B (OR): 3.3, p=0.04). CONCLUSION: Our findings show that obese children and adolescents have higher rates of ADHD symptoms and problems in peer relations. Underestimation of ADHD might be a risk factor for treatment failure in obesity since ADHD symptoms cause a lack of motivation and compliance.

Pubertal development of Turkish children.

AIM: To investigate the pubertal development of Turkish school children, to look for possible secular trends in pubertal development. METHODS: 1,562 girls and 1,749 boys (aged 6-16.5 years) from urban and rural schools were studied. Weight and height were measured and body mass index was calculated. Pubertal stages were assessed according to Tanner. Testicular volume was determined using an orchidometer. Menarcheal age was recorded. RESULTS: In girls, mean ages at breast stage (B) were 7.74 +/- 1.08 years for B1, 10.16 +/- 0.97 for B2, 11.72 +/- 1.29 for B3, 12.97 +/- 1.17 for B4, and 13.66 +/- 0.89 for B5. Mean ages at pubic hair stage (PH) were 8.72 +/- 1.50 years for PH1, 10.57 +/- 1.39 for PH2, 12.12 +/- 1.10 for PH3, 13.10 +/- 1.04 for PH4, and 13.87 +/- 0.83 for PH5. Mean age at menarche was 12.41 years. Menarcheal age was earlier in overweight and obese children compared with that in normal children. In boys, mean ages at each maturity stage according to testis volume (G) were 8.70 +/- 1.38 years for G1, 11.76 +/- 1.28 for G2, 12.81 +/- 1.0 for G3, 13.17 +/- 0.87 for G4, and 13.87 +/- 0.98 for G5. Mean ages at PH in boys were 9.39 +/- 1.81 years for PH1, 12.02 +/- 1.33 for PH2, 13.05 +/- 0.88 for PH3, 13.42 +/- 0.87 for PH4, and 14.02 +/- 0.92 for PH5. CONCLUSIONS: The current study provides an up-to-date reference of normal sexual maturation of Turkish children. While the mean age at onset of puberty in boys was comparable to that of other populations in the world, girls were found to start pubertal development earlier than in other populations.

Two cases of Cushing's syndrome due to overuse of topical steroid in the diaper area.

Topical use of corticosteroids may cause immunosuppression and iatrogenic Cushing's syndrome via hypothalamic-pituitary-adrenal axis. We report two cases with iatrogenic Cushing's syndrome with different clinical outcomes due to abuse of same potent topical steroid clobetasol propionate. One of them died because of fatal disseminated cytomegalovirus infection. The other patient recovered completely. Physicians and parents should be informed about the adverse effects of such potent topical corticosteroids and physicians should prescribe less potent agents, especially during infancy.

Are C-reactive protein and homocysteine cardiovascular risk factors in obese children and adolescents?

BACKGROUND: Several prospective epidemiological studies have demonstrated that high-sensitivity C-reactive protein (hsCRP) and plasma homocysteine (hcy) are predictors of future coronary events among healthy men and women. The aim of the present study was therefore to investigate a possible relationship between hsCRP, hcy levels and body mass index (BMI), relative weight (RW), serum leptin levels, and cardiovascular risk factors in obese children and adolescents. METHODS: The study involved 28 obese children and adolescents (13 girls, 15 boys; BMI>95 per thousand for age and sex), 4.5-15 years of age (mean 10.7 +/- 0.6 years), who attended hospital for a basic obesity check-up. The association between hsCRP, hcy levels and BMI, RW, serum leptin levels, and cardiovascular risk factors such as blood pressure (BP), lipid profile, serum fasting insulin levels, and insulin resistance indexes, was investigated. RESULTS: Serum hsCRP level was positively correlated with BMI (r = 0.512, P < 0.01), RW (r = 0.438, P < 0.05), systolic and diastolic BP (r = 0.498, P < 0.01), serum leptin levels (r = 0.457, P < 0.05), but not with serum lipid, glucose, fasting insulin, plasma hcy levels or insulin resistance indexes. For hcy level, in contrast, no correlation was found with BMI, RW, systolic and diastolic BP, serum lipid levels, leptin, hsCRP, glucose, fasting insulin levels, or insulin resistance indexes. CONCLUSIONS: hsCRP is correlated with BMI, RW, BP and leptin, which are risk factors for coronary heart disease, which supports the relationship between obesity, inflammation and atherosclerosis. hsCRP in childhood obesity might be a useful index to predict possible atherosclerotic events.

Body fat distribution in childhood obesity: association with metabolic risk factors.

OBJECTIVES: To evaluate the clinical significance of body fat distribution in childhood obesity, we investigated the associations of subcutaneous and intraabdominal (preperitoneal and visceral) fat, estimated by ultrasonography, with metabolic risk factors. SUBJECTS: Fifty-one obese (age 11.5+/- 2.6 years) and 33 non-obese (age 12.2+/- 2.7 years) children. STUDY DESIGN: Case control study. METHODS: Ultrasonographic measurements of fat thickness [maximum and minimum preperitoneal fat thicknesses (Pmax, Pmin), maximum and minimum subcutaneous fat thicknesses (Smax, Smin), visceral fat thickness (V), triceps (Tr) and subscapular (Ss) skin fold thicknesses] were documented. Blood pressures, lipid profiles, fasting insulin levels, glucose/insulin ratio and HOMA IR (homeostasis model assessment for insulin resistance) were evaluated in both groups and these parameters were correlated with body fat distribution. RESULTS: In the obese group, fasting insulin level was correlated to Smin, Smax, and Pmin. HOMA, accordingly, was also correlated to Smin, Smax, and Pmin. Fasting insulin level and HOMA showed no correlation with either Pmax or visceral fat thickness. ANALYSIS: Abdominal subcutaneous fat thickness measurements were the best predictors of hyperinsulinemia (R2: 0.32). CONCLUSION: We did not observe a significant correlation between blood pressure, lipid parameters and body fat distribution in obese group. Abdominal subcutaneous fat thickness might be a better predictor of the risk for hyperinsulinemia in childhood obesity.

Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

Seizures and diagnostic difficulties in hyperinsulinism-hyperammonemia syndrome.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare disorder presented with recurrent hypoglycemia and elevated serum ammonia, which may lead to development delays, permanent neurologic damages, if it remains underdiagnosed. It is caused by activating mutations in the GLUD1 gene which encodes the intra-mitochondrial enzyme glutamate dehydrogenase (GDH). HI/HA syndrome is considered the second most common form of hyperinsulinism (HI), and usually associated with epileptic seizures, mental retardation and generalized dystonia. We reported a patient who was diagnosed as HI/HA with multiple episodes of seizures; and previously had been diagnosed and treated for epilepsy. She has heterozygous mutation in GLUD1 gene. Treatment with diazoxide enabled complete resolution of the seizures. One year later, when her brother was six months old, he was also diagnosed with HI/HA. Later, the same mutation of GLUD1 was detected in both her father and brother too.

Pseudohypoaldosteronism type 1 and respiratory distress syndrome.

We present a patient born at 31 weeks gestation with respiratory distress syndrome (RDS) which did not respond to surfactant. He also developed hyponatremia, hyperkalemia and dehydration with increased sweat electrolytes despite high levels of serum aldosterone, thus systemic pseudohypoaldosteronism type 1 (PHA-1) diagnosis was made. Systemic PHA-1 is caused by mutations of amiloride-sensitive epithelial sodium channel (ENaC) genes. Because ENaC is a rate-limiting step for sodium absorption by epithelial cells, not only of the renal tubule but also of the lung epithelium, patients with PHA-1 with pulmonary symptoms have sometimes been reported. However, our patient appears to be the second reported human case of both neonatal RDS and PHA-1, and the first description, with increased sweat electrolytes, of a premature baby with systemic PHA-1 and RDS.