Congenital Adrenal Hyperplasia (CAH) and Gitelman Syndrome (GS): Overlapping Symptoms in an Uncommon Association

Background. Classical salt-wasting (SW) congenital adrenal hyperplasia (CAH) and Gitelman syndrome (GS) are two genetic conditions in which dyselectrolytemia may occur. No association between the two conditions has been previously described. Case Presentation. We present the case of a boy with a neonatal diagnosis of SW-CAH who showed low potassium blood levels from the age of 15 years. This electrolytic alteration was, at first, attributed to an excessive action of mineralocorticoid drugs. Due to persistence of hypokalemia, SLC12A3 whole genome sequencing was performed, showing a heterozygous C to T base pair substitution at position 965 in gene SLC12A3. This mutation is related to Gitelman syndrome with autosomal recessive transmission. Conclusions. SW-CAH and GS determine opposite values of potassium in the absence of specific therapy, with a natural tendency to compensate each other. The symptom overlap makes diagnosis difficult. Organic causes of hypokalemia in patients undergoing life-saving therapy should not be excluded.

Maternal anti-Toxoplasma Treatment during Pregnancy is Associated with Reduced Sensitivity of Diagnostic Tests for Congenital Infection in the Neonate

Neonatal diagnosis of congenital toxoplasmosis is based on the combination of serological and molecular tests. Maternal screening and treatment differ according to national policies, and may impact on the sensitivity of diagnostic methods in infants at birth. In this multicenter study, 115 neonates born to 61 treated (53%) and 54 (47%) untreated women were retrospectively included in three centers (France, Serbia, USA) to assess the impact of maternal anti-Toxoplasma treatment on the performance of neonatal workup at birth (neosynthesized anti-Toxoplasma IgM, IgA and IgG, and qPCR), using univariate and multivariate approaches. Independently of the time of maternal seroconversion, the serological techniques were differently impacted by maternal treatment. The detection of IgM by ISAGA and western-blot (WB) dropped from 90.7% and 88.2% in untreated neonates to 53.3% and 51.9% in treated neonates (p<0.05), whereas IgM ELISA and IgA ISAGA were not significantly affected by maternal treatment. A 2-fold reduction in the sensitivity of neosynthesized IgG by WB was also observed in case of treatment during pregnancy (37.7% versus 82.3%). Interestingly, the effect of treatment was shown to be duration-dependent, especially for IgM detection, when treatment course exceeded 8 weeks, whatever the therapy. The sensitivity of Toxoplasma PCR in blood was also lowered by maternal treatment from 39.1% to 23.2%. These results highlight that anti-Toxoplasma therapy during pregnancy may set back biological evidences of neonatal infection at birth, and underline the need for a careful serological follow-up of infants with normal workup.