Abstract: Newborn screening (NBS) for inherited metabolic diseases (IMDs) substantially shortens a patient's journey. It enables the early start of metabolic treatment which might prevent potentially lethal neonatal disease manifestations, while promoting favorable development and long-term clinical outcomes. This study aims to assess growth in screened individuals with IMDs under different dietary regimes. Anthropometric data (3585 prospective measures) of 350 screened individuals with IMDs born between 1999 and 2018 and participating in a German prospective multi-center observational study were evaluated. Overall, birth measures were within the reference ranges, suggesting unaffected prenatal growth, except for phenylketonuria (weight) and glutaric aciduria type 1 (head circumference). After birth, longitudinal analysis of anthropometric measures revealed a loss of height SDS (-0.5 SDS; P0.0001), head circumference SDS (-0.2 SDS; P=0.0028), but not for weight SDS (0.1 SDS; P=0.5097) until the age of 18 years, while BMI SDS increased (0.4 SDS; P0.0001). The significant interaction with age and diet groups was pronounced for the linear growth in individuals receiving diets being low in protein, long-chain triglycerides and galactose (p

Abstract: The SARS-CoV2 pandemic challenges health care systems worldwide. Within inherited metabolic disorders (IMDs) the vulnerable subgroup of intoxication-type IMDs such as organic acidurias (OA) and urea cycle disorders (UCD) show risk for infection-induced morbidity and mortality. This study (observation period February 2020 to December 2021) evaluates impact on medical health care as well as disease course and outcome of SARS-CoV2-infections in patients with intoxication-type IMDs managed by participants of the European Registry and Network for intoxication type metabolic diseases Consortium (E-IMD). Survey's respondents managing 792 patients (n=479 pediatric; n=313 adult) with intoxication-type IMDs (n=454 OA; n=338 UCD) in 14 countries reported on 59 (OA: n=36; UCD: n=23), SARS-CoV2-infections (7.4%). Medical services were increasingly requested (95%), mostly alleviated by remote technologies (86%). Problems with medical supply were scarce (5%). Regular follow-up visits were reduced in 41% (range 10-50%). Most infected individuals (49/59; 83%) showed mild clinical symptoms, while 10 patients (17%; n=6 OA including four transplanted MMA patients; n=4 UCD) were hospitalized (metabolic decompensation in 30%). ICU treatment was not reported. Hospitalization rate did not differ for diagnosis or age group (p=0.778). Survival rate was 100%. Full recovery was reported for 100% in outpatient care and 90% of hospitalized individuals. SARS-CoV-2 impacts health care of individuals with intoxication-type IMDs worldwide. Most infected individuals, however, showed mild symptoms and did not require hospitalization. SARS-CoV2-induced metabolic decompensations were usually mild without increased risk for ICU treatment. Overall prognosis of infected individuals is very promising and IMD-specific or COVID-19-related complications have not been observed

Abstract: Analytical and therapeutic innovations led to a continuous but variable extension of newborn screening (NBS) programmes worldwide. Every extension requires a careful evaluation of feasibility, diagnostic (process) quality and possible health benefits to balance benefits and limitations. The aim of this study was to evaluate the suitability of 18 candidate diseases for inclusion in NBS programmes. Utilising tandem mass spectrometry as well as establishing specific diagnostic pathways with second-tier analyses, three German NBS centres designed and conducted an evaluation study for 18 candidate diseases, all of them inherited metabolic diseases. In total, 1 777 264 NBS samples were analysed. Overall, 441 positive NBS results were reported resulting in 68 confirmed diagnoses, 373 false-positive cases and an estimated cumulative prevalence of approximately 1 in 26 000 newborns. The positive predictive value ranged from 0.07 (carnitine transporter defect) to 0.67 (HMG-CoA lyase deficiency). Three individuals were missed and 14 individuals (21%) developed symptoms before the positive NBS results were reported. The majority of tested candidate diseases were found to be suitable for inclusion in NBS programmes, while multiple acyl-CoA dehydrogenase deficiency, isolated methylmalonic acidurias, propionic acidemia and malonyl-CoA decarboxylase deficiency showed some and carnitine transporter defect significant limitations. Evaluation studies are an important tool to assess the potential benefits and limitations of expanding NBS programmes to new diseases