B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values

A Multicenter Experience with Long-Acting Somatostatin Analogues in Patients with Congenital Hyperinsulinism

Background/Aims: Congenital hyperinsulinism (CHI) is a rare disease characterized by recurrent severe hypoglycemia. In the diffuse form of CHI, pharmacotherapy is the preferred choice of treatment. Long-acting somatostatin analogues have been used in children as off-label medication. However, the efficacy, outcomes, and adverse effect profiles of long-acting somatostatin analogues have not been described in multicentered studies. The aim of this retrospective study is to summarize the experience with long-acting somatostatin analogues in a large group of children with CHI. Methods: Data were obtained retrospectively from 27 patients with CHI who received long-acting somatostatin analogues in 6 different centers in Europe. These included information on glycemic stability, auxology, and adverse effect profile in clinical follow-up assessments. Results: Blood glucose control improved in most patients (89%). No life-threatening side effects occurred. Thirteen patients (48%) experienced side effects; in 3 patients (11%), the side effects were the main reason for discontinuation of the treatment. The most frequent side effect was elevated liver enzymes (n = 10, 37%). Conclusion: Long-acting somatostatin analogues are effective in glycemic control of patients with CHI. However, in 37% of all patients increased liver enzymes were observed. It is important to monitor liver function in all patients receiving long-acting somatostatin analogue therapy. (C) 2017 S. Karger AG, Base

Evaluation of the Dutch neonatal screening for congenital adrenal hyperplasia

Background In 2002, a nationwide screening for congenital adrenal hyperplasia (CAH) was introduced in the Netherlands. The aim of our study is to evaluate the validity of the neonatal screening for CAH and to assess how many newborns with salt-wasting (SW) CAH have already been clinically diagnosed before the screening result was known. Methods Retrospective, descriptive study. The following data of patients with positive screening results since implementation of the screening programme were collected (1 January 2002 up until 31 December 2013): gestational age, sex, diagnosis, clinical presentation and contribution of screening to the diagnosis. Results In the evaluated period, 2 235 931 newborns were screened. 479 children had an abnormal screening result, 133 children were diagnosed with CAH (114 SW, 14 simple virilizing (SV)), five non-classic CAH. During this period, no patients with SW CAH were missed by neonatal screening (sensitivity was 100%). After exclusion of 17 cases with missing information on diagnosis, specificity was 99.98% and positive predictive value was 24.7%. Most false positives (30%) were attributable to prematurity. Of patients with SW CAH, 68% (71/104) patients were detected by neonatal screening and 33 (33/104) were clinically diagnosed. Of girls with SW CAH, 38% (14/37) were detected by neonatal screening and 62% (23/37) were clinically diagnosed. Conclusion The Dutch neonatal screening has an excellent sensitivity and high specificity. Both boys and girls can benefit from neonatal screening

Evaluation of the Dutch neonatal screening for congenital adrenal hyperplasia

Background: In 2002, a nationwide screening for congenital adrenal hyperplasia (CAH) was introduced in the Netherlands. The aim of our study is to evaluate the validity of the neonatal screening for CAH and to assess how many newborns with salt-wasting (SW) CAH have already been clinically diagnosed before the screening result was known. Methods: Retrospective, descriptive study. The following data of patients with positive screening results since implementation of the screening programme were collected (1 January 2002 up until 31 December 2013): gestational age, sex, diagnosis, clinical presentation and contribution of screening to the diagnosis. Results: In the evaluated period, 2 235 931 newborns were screened. 479 children had an abnormal screening result, 133 children were diagnosed with CAH (114 SW, 14 simple virilizing (SV)), five non-classic CAH. During this period, no patients with SW CAH were missed by neonatal screening (sensitivity was 100%). After exclusion of 17 cases with missing information on diagnosis, specificity was 99.98% and positive predictive value was 24.7%. Most false positives (30%) were attributable to prematurity. Of patients with SW CAH, 68% (71/104) patients were detected by neonatal screening and 33 (33/104) were clinically diagnosed. Of girls with SW CAH, 38% (14/37) were detected by neonatal screening and 62% (23/37) were clinically diagnosed. Conclusion: The Dutch neonatal screening has an excellent sensitivity and high specificity. Both boys and girls can benefit from neonatal screening

Second-tier testing for 21-hydroxylase deficiency in the Netherlands; a newborn screening pilot study.

BACKGROUND: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cut-off values. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false-positives. We assessed the accuracy and turnaround time of the current CAH NBS-algorithm and compared this to alternative algorithms by performing a second-tier 21-deoxycortisol (21-DF) pilot-study. METHODS: Dried blood spots (DBS) of newborns with inconclusive and positive 17-OHP (immunoassay) first HP results were sent from regional NBS laboratories to the Amsterdam UMC Endocrine Laboratory. In 2017-2019 21-DF concentrations were analyzed by liquid chromatography-tandem mass spectrometry, in parallel with routine NBS. Diagnoses were confirmed by mutation analysis. RESULTS: 328 DBS were analyzed. 37 newborns had confirmed classic CAH, 33 were false-positive and 258 were categorized as negative in the second HP following the current algorithm. In the second-tier, all 37 confirmed CAH had elevated 21-DF concentrations, all 33 false-positives and 253/258 second HP negatives had undetectable 21-DF concentrations. The elevated 21-DF of the other five newborns may be NBS false-negatives or second-tier false-positives. Adding the second-tier to inconclusive first HPs reduced the number of false-positives to 11 and prevented all 286 second HPs. Adding the second-tier to both positive and inconclusive first HPs eliminated all false-positives at the cost of delayed referral for 31 CAH patients (1-4 days). CONCLUSION: Application of the second-tier 21-DF measurement to inconclusive first HPs improved our CAH NBS by reducing false-positives, abolishing the second HP and thereby shortening referral time

Treatment of congenital adrenal hyperplasia in children aged 0–3 years: A retrospective multicenter analysis of salt supplementation, glucocorticoid and mineralocorticoid medication, growth and blood pressure

Objectives: International guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed. Aim: To investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0–3 years. Methods: Retrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months. Results: We analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5–4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95. Conclusion: In children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life