Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries.

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet.

Simplification of Dietary Treatment in Pharmacoresistant Epilepsy: Impact of C8 and C10 Fatty Acids on Sirtuins of Neuronal Cells In Vitro.

Pharmacotherapy is the therapeutic mainstay in epilepsy; however, in about 30% of patients, epileptic seizures are drug-resistant. A ketogenic diet (KD) is an alternative therapeutic option. The mechanisms underlying the anti-seizure effect of a KD are not fully understood.

Brain function in classic galactosemia, a galactosemia network (GalNet) members review.

Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge.

LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in the HARP cohort.

Unlabelled: Soluble RANKL (sRANKL) and osteoprotegerin (OPG) are regulators of osteoclast differentiation and activation, but adequate pediatric reference values are lacking. Here we provide LMS (Lambda-Mu-Sigma)-based continuous pediatric reference percentiles for sRANKL, OPG and sRANKL/OPG ratio that will allow calculation of standardized patient z-scores to assess bone modeling in children.

Purpose: Soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) are regulators of osteoclast differentiation and activation and thus bone metabolic turnover in children.

LMS-Based Pediatric Reference Values for Parameters of Phosphate Homeostasis in the HARP Cohort.

Context: The assessment of phosphate homeostasis in children is challenging due to the marked changes in laboratory parameters during growth and development, and the lack of adequate reference values.

Objective: To develop Lambda-Mu-Sigma (LMS)-based continuous pediatric reference percentiles for 7 key laboratory parameters of phosphate homeostasis.

Methods: This cross-sectional, single-center study, the HAnnover Reference values for Pediatrics (HARP) study, included 455 children aged 0.

From common to rare: repurposing of bempedoic acid for the treatment of glycogen storage disease type 1.

Hypoketotic hypoglycaemia is a biochemical hallmark of glycogen storage disease type 1 (GSD1). This is due to inhibition of carnitine-palmitoyl transferase 1 by malonyl-CoA. This inhibits the influx of long-chain fatty acids into the mitochondrial matrix for fatty acid oxidation.

Collaborative evaluation study on 18 candidate diseases for newborn screening in 1.77 million samples.

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.

Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants.

Purpose: This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and determine the role of cysteine supplementation in its treatment.

Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied within an international retrospective collection of de-identified patient data.

Results: In 62 individuals, including 30 previously unreported cases, we described 47 (likely) pathogenic TRMU variants, of which 17 were novel, and 1 intragenic deletion.

Impact of pregnancy planning and preconceptual dietary training on metabolic control and offspring's outcome in phenylketonuria.

To prevent maternal phenylketonuria (PKU) syndrome low phenylalanine concentrations (target range, 120-360 μmol/L) during pregnancy are recommended for women with PKU. We evaluated the feasibility and effectiveness of current recommendations and identified factors influencing maternal metabolic control and children's outcome. Retrospective study of first successfully completed pregnancies of 85 women with PKU from 12 German centers using historical data and interviews with the women.

Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients.

Cystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10-20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis.

Possible role of SIRT1 and SIRT3 in post-translational modifications in human breast milk during the neonatal period.

We measured free and proteinic concentrations of native and modified amino acids from post-translational modifications (PTMs) and correlated them with the activity of SIRT1 and SIRT3 in the pellet and aqueous phases of human breast milk samples of ten lactating women during the neonatal period. SIRT1 and SIRT3 correlated directly with citrullination, asymmetric dimethylation and glycation of L-arginine, hydroxylation and glycation of L-lysine. SIRT1 and SIRT3 correlated inversely with the hydroxylation of L-proline.

Predictors of growth patterns in children with mucopolysaccharidosis I after haematopoietic stem cell transplantation.

Mucopolysaccharidosis type I (MPS I) is an autosomal-recessive metabolic disorder caused by an enzyme deficiency of lysosomal alpha-l-iduronidase (IDUA). Haematopoietic stem cell transplantation (HSCT) is the therapeutic option of choice in MPS I patients younger than 2.5 years, which has a positive impact on neurocognitive development.

Treatment of Fabry Disease management with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).

Aims: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL), resulting in the lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacological chaperone increasing endogenous AGAL activity. In this prospective observational multicentre study, safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under 'real-world' conditions.

A SUMO4 initiator codon variant in amyotrophic lateral sclerosis reduces SUMO4 expression and alters stress granule dynamics.

Background: Recent evidence points toward a role of the small ubiquitin-like modifier (SUMO) system, including SUMO4, in protecting from stress insults and neurodegeneration, such as the progressive motor neuron disease amyotrophic lateral sclerosis (ALS), e.g., by regulating stress granule (SG) dynamics.

Serum N-glycomics of a novel CDG-IIb patient reveals aberrant IgG glycosylation.

Rare genetic mutations of the mannosyl-oligosaccharide glucosidase (MOGS) gene affecting the function of the mannosyl-oligosaccharide glucosidase (glucosidase I) are the cause of the congenital disorder of glycosylation IIb (CDG-IIb). Glucosidase I specifically removes the distal α1,2-linked glucose from the protein bound precursor N-glycan Glc3Man9GlcNAc2, which is the initial step of N-glycan maturation. Here, we comparatively analyzed N-glycosylation of the whole serum proteome, serum-derived immunoglobulin G (IgG), transferrin (TF), and α-1-antitrypsin (AAT) of a female patient who is compound heterozygous for 2 novel missense mutations in the MOGS gene, her heterozygous parents, and a sibling with wildtype genotype by multiplexed capillary gel electrophoresis coupled to laser induced fluorescence detection (xCGE-LIF) at unprecedented depth.

Impact of Dietary Modifications on Plasma Sirtuins 1, 3 and 5 in Older Overweight Individuals Undergoing 12-Weeks of Circuit Training.

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that regulate numerous pathways such as mitochondrial energy metabolism in the human body. Lower levels of these enzymes were linked to diseases such as diabetes mellitus and were also described as a result of aging. Sirtuins were previously shown to be under the control of exercise and diet, which are modifiable lifestyle factors.

The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study.

The aim of the study was a systematic evaluation of cognitive development in individuals with glutaric aciduria type 1 (GA1), a rare neurometabolic disorder, identified by newborn screening in Germany. This national, prospective, observational, multi-centre study includes 107 individuals with confirmed GA1 identified by newborn screening between 1999 and 2020 in Germany. Clinical status, development, and IQ were assessed using standardized tests.

A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C.

Background: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC).

Methods: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003-2018). Diagnosis was made by filipin skin test or genetic testing.

Cross-sectional analysis: clinical presentation of children with persistently low ALP levels.

Objectives: Low activity of serum alkaline phosphatase (ALP) is a hallmark of hypophosphatasia (HPP), but low readings of ALP are not always recognized in clinical routine. Understanding the clinical presentations associated with low ALP may contribute to a timelier diagnosis of HPP.

Methods: Data from paediatric patients with low ALP, excluding patients in intensive care and with oncological/haematological disorders, were analysed.

Analysis of Sirtuin 1 and Sirtuin 3 at Enzyme and Protein Levels in Human Breast Milk during the Neonatal Period.

Breast feeding is regarded as the preferred nutrition modality for children during the first few months of life. It not only furthers growth and development but also is supposed to impact later life. The first 1000 days are regarded as a critical window for development, even beyond infancy.

Long-term safety and outcomes in hereditary tyrosinaemia type 1 with nitisinone treatment: a 15-year non-interventional, multicentre study.

Background: Since the EU approval of nitisinone in 2005, prognosis for patients with hereditary tyrosinaemia type 1 has changed dramatically, with patients living with the disease now reaching adulthood for the first time in history. This study aimed to assess the long-term safety and outcomes of nitisinone treatment in patients with hereditary tyrosinaemia type 1.

Methods: We did a non-interventional, non-comparative, multicentre study in 77 sites across 17 countries in Europe and collected retrospective and prospective longitudinal data in patients with hereditary tyrosinaemia type 1 who were treated with oral nitisinone during the study period (Feb 21, 2005, to Sept 30, 2019).