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This study aimed to estimate the number of infants who died of unrecognized congenital adrenal hyperplasia (CAH) in Austria and the Czech Republic within the past 13 years, before the introduction of adequate neonatal screening. The study was based on retrospective analysis of neonatal screening cards of 242 infants who died suddenly between 7 days and 12 months of age and whose cause of death could not be identified. 17-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay and positive samples were subsequently genotyped. Three infants out of 242 may have had unrecognized CAH due to CYP21 (steroid 21-hydroxylase) gene defect. Their newborn 17-OHP levels and CYP21 genotypes were 706 nmol/l and del/conv//del/conv, 53 nmol/l and I2//I2, and 811 nmol/l and I2//Gln318stop, respectively. CAH due to CYP21 defect can lead to sudden unexpected death without prior symptoms typical for the condition. Hence, newborn screening would have prevented these deaths had it been available. In addition, we have shown that the I2 point mutation that is expected to lead to simple virilizing form may lead to a fatal outcome. [ABSTRACT FROM AUTHOR]

Neonatal screening for congenital primary hypothyroidism (CH) may not distinguish between transient (TCH) and permanent dysfunction (PCH), causing potential overtreatment and concerns in affected families. To specify the indication for interruption of therapy, we analysed the German registry "HypoDok" for infants with CH, which oversees 1625 patients from 49 participating centres in Germany and Austria from 1997 until today. A total of 357 patients with a thyroid gland in loco typico were identified and retrospectively grouped according to cessation (TCH, n = 24) or continuation (PCH, n = 333) of L-thyroxine (L-T 4 ) treatment at 2 years of age. The receiver operating characteristic (ROC) analysis was performed to identify cutoffs predicting TCH by screening TSH concentrations and L-T 4 dosages. Gestational ages, birth weights and prevalence of associated malformations were comparable in both groups. The cutoff screening TSH concentration was 73 mU/L. The cutoff daily L-T 4 dosage at 1 year was 3.1 μg/kg (90% sensitivity, 63% specificity; 36 μg/day) and at 2 years of age 2.95 μg/kg (91% sensitivity, 59% specificity; 40 μg/day). At 2 years of age, specificity (71%) increased when both of these parameters were considered together.Conclusion: The decision to continue or cease L-T 4 treatment at 2 years of age in CH patients diagnosed in neonatal screening may be based on their screening TSH concentrations and individual L-T 4 dosages at 1 and 2 years of age. Thus, TCH and PCH may be distinguished; overtreatment avoided; and affected families reassured. What is Known: • The course of congenital primary hypothyroidism may be transient, causing potential overtreatment. • The dose of l-thyroxine at 1 or 2 years of age may predict a transient course of primary congenital hypothyroidism. What is New: • TSH screening concentration and l-thyroxine dosages at 1 and 2 years of age represent reliable predictors for transient congenital primary hypothyroidism with higher sensitivity and specificity when considered together in order to select eligible patients who qualify for treatment withdrawal., (© 2021. The Author(s).)

Unlabelled: Newborn screening for biotinidase deficiency (BD) provides prevention of neurological sequelae in patients with low residual enzyme activity by early treatment with oral biotin substitution. Screening 1.1 million newborns in Austria and consecutive family studies led to the identification of 21 patients with profound BD (residual activity <10%) (incidence: 1:59,800) and to 12 patients with partial BD (residual activity 10%-30%) (incidence 1:89,700). Application of an HPLC assay using the natural substrate biocytin allowed exact quantification of extremely low residual biotinidase activities and thus subdivision of patients with profound BD into a group with a residual activity 0%-1% of normal activity (n = 5) and >1%-<10% (n = 16) respectively. Evaluation of clinical and neuropsychological outcome showed that only patients with a biotinidase activity < 1% (n = 3/5) exhibited characteristic clinical symptoms within the first weeks of life, while five patients with a residual activity of 1.2%-4.6% did not develop clinical symptoms even when not treated until 3.5 21 years. In all patients with residual activity <10% and biotin substitution within the first weeks of life, neuropsychological outcome was normal, while abnormal in three out of five patients tested for IQ and treated after the age of 3.5 years. In five out of nine patients with poor compliance or delayed or no treatment, visual and brainstem auditory evoked potentials were measured and were within age-related normal values. All patients with partial BD available for follow-up remained clinically and neuropsychologically asymptomatic without treatment at ages 2.5 10 years., Conclusion: The incidence of biotinidase deficiency in Austria is comparable to other European countries. Subdivision of the group of patients with profound biotinidase deficiency suggests that only patients with residual activities < 1% are prone to develop clinical symptoms early in life, while patients with residual activities >1% may remain asymptomatic even without treatment, as do patients with partial deficiency. Moderate mental retardation might represent a possible manifestation of cerebral dysfunction in patients with profound biotinidase deficiency.