Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors.

Argininosuccinate lyase deficiency (ASLD) is a recessive metabolic disorder caused by variants in ASL. In an essential step in urea synthesis, ASL breaks down argininosuccinate (ASA), a pathognomonic ASLD biomarker. The severe disease forms lead to hyperammonemia, neurological injury, and even early death.

European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children.

Several high-risk medical devices for children have become unavailable in the European Union (EU), since requirements and costs for device certification increased markedly due to the EU Medical Device Regulation. The EU-funded CORE-MD project held a workshop in January 2023 with experts from various child health specialties, representatives of European paediatric associations, a regulatory authority and the European Commission Directorate General Health and Food Safety. A virtual follow-up meeting took place in March 2023.

Availability and use of rapid diagnostic tests for the management of acute childhood infections in Europe: A cross-sectional survey of paediatricians.

Background: Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability.

Methods And Findings: A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks.

The Finnish genetic heritage in 2022 - from diagnosis to translational research.

Isolated populations have been valuable for the discovery of rare monogenic diseases and their causative genetic variants. Finnish disease heritage (FDH) is an example of a group of hereditary monogenic disorders caused by single major, usually autosomal-recessive, variants enriched in the population due to several past genetic drift events. Interestingly, distinct subpopulations have remained in Finland and have maintained their unique genetic repertoire.

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.

CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy.

Hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) is a severe recessive inherited disease, causing muscular degeneration and retinochoroidal atrophy that progresses to blindness. HOGA arises from mutations in the ornithine aminotransferase gene, and nearly one-third of the known patients worldwide are homozygous for the Finnish founder mutation OAT c.1205 T > C p.

An eHealth Framework for Managing Pediatric Growth Disorders and Growth Hormone Therapy.

Background: The use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder.

Objective: Our objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy.

Connected health for growth hormone treatment research and clinical practice: learnings from different sources of real-world evidence (RWE)-large electronically collected datasets, surveillance studies and individual patients' cases.

Background: A range of factors can reduce the effectiveness of treatment prescribed for the long-term management of chronic health conditions, such as growth disorders. In particular, prescription medications may not achieve the positive outcomes expected because approximately half of patients adhere poorly to the prescribed treatment regimen.

Methods: Adherence to treatment has previously been assessed using relatively unreliable subjective methods, such as patient self-reporting during clinical follow-up, or counting prescriptions filled or vials returned by patients.

Motivational Interviewing and Glycemic Control in Adolescents With Poorly Controlled Type 1 Diabetes: A Randomized Controlled Pilot Trial.

A multicenter randomized controlled pilot trial investigated whether motivational interviewing (MI) by diabetes physicians improves glycemic control and variability in the context of follow-up for adolescent patients with poorly controlled type 1 diabetes. Patients ( = 47) aged 12 to 15.9 years who showed poor glycemic control (HbA1c >75 mmol/mol/9.

Adrenal function after induction therapy for acute lymphoblastic leukemia in children short: adrenal function in ALL.

Prednisolone used in the induction phase of the treatment of acute lymphoblastic leukemia (ALL) may suppress hypothalamic-pituitary-adrenal axis and require hydrocortisone substitution. In this retrospective analysis, we reviewed altogether 371 ACTH stimulation tests of 352 children after a uniform NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL induction. Both low- and standard-dose ACTH tests were used.

Stress-Dose Corticosteroid Versus Placebo in Neonatal Cardiac Operations: A Randomized Controlled Trial.

Background: Corticosteroids can improve the hemodynamic status of neonates with postoperative low cardiac output syndrome after cardiac operations. This study compared a prophylactically administered stress-dose corticosteroid (SDC) regimen against placebo on inflammation, adrenocortical function, and hemodynamic outcome.

Methods: Forty neonates undergoing elective open heart operations were randomized into two groups.

Incidence and outcome of epilepsy syndromes with onset in the first year of life: A retrospective population-based study.

Objective: Population-based studies on infantile epilepsy syndromes are scarce. Our aim was to provide syndrome-specific data on the incidence and outcome of epilepsy in a population-based cohort of infants with epilepsy onset in the first year.

Methods: Included were all infants born in 1997 through 2006 whose epileptic seizures started before 12 months of age and who were residents of the Helsinki University Hospital district at the time of seizure onset.

Earlier diagnosis and strict diets improve the survival rate and clinical course of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

Aim: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a severe metabolic disease that, without treatment, often leads to premature death or serious handicap. The aim of this study was to evaluate the clinical course of LCHADD with the homozygous 1528G>C (E510Q) mutation when patients underwent strict dietary treatment.

Methods: From 1997 to 2010, 16 patients with LCHADD were diagnosed in Finland.

Peripheral neuropathy in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency - A follow-up EMG study of 12 patients.

Background: The neonatal screening and early start of the dietary therapy have improved the outcome of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). The acute symptoms of LCHADD are hypoketotic hypoglycemia, failure to thrive, hepatopathy and rhabdomyolysis. Long term complications are retinopathy and neuropathy.

LMNA Mutation c.917T>G (p.L306R) Leads to Deleterious Hyper-Assembly of Lamin A/C and Associates with Severe Right Ventricular Cardiomyopathy and Premature Aging.

Mutations in the LMNA gene coding for the nuclear lamina proteins lamin A and its smaller splice form lamin C associate with a heterogeneous group of diseases collectively called laminopathies. Here, we describe a 2-year-old patient with a previously undescribed phenotype including right ventricular cardiomyopathy, progeroid features, and premature death. Sequencing of LMNA revealed a novel heterozygous de novo mutation p.

Patients with organic acidaemias have an altered thiol status.

Aim: To study whether patients with organic acidaemias have altered glutathione (GSH) levels and thiol redox status. Previously, organic acidaemias have been associated with mitochondrial dysfunction and oxidative stress, suggesting an increased need for antioxidant protection. Furthermore, dietary protein restriction may impair GSH synthesis in these diseases.

Plasma thiol status is altered in children with mitochondrial diseases.

Objective: This study was undertaken to investigate thiol metabolism as a marker of oxidative stress and antioxidative defence capacity in a cohort of children with biochemically and/or genetically confirmed mitochondrial disease. Previous studies suggest that lower glutathione levels, which have been shown to further compromise mitochondrial function, may occur in these diseases. Better understanding of the pathogenesis of mitochondrial diseases is important in order to improve their treatment.

GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1.

Context: KISS1 is a candidate gene for GnRH deficiency.

Objective: Our objective was to identify deleterious mutations in KISS1.

Patients And Methods: DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions.

Change in plasma and erythrocyte thiol levels in children undergoing fasting studies for investigation of hypoglycaemia.

Introduction: It is unclear how repeated episodes of HG cause brain injury, but oxidative stress has been suggested to play a role. Non-protein thiols (glutathione, GSH, and cysteine, CYSH) form an important antioxidant defence, and their redox state is dependent on intracellular energy supplies and reducing power which are possibly compromised during low blood glucose concentrations.

Aim Of Study: To study thiol status in children undergoing investigations for hypoglycaemia .

Growth hormone therapy is safe and effective in patients with lysinuric protein intolerance.

Background: Lysinuric protein intolerance (LPI) is an autosomal recessive cationic amino acid transport defect characterized by episodes of postprandial hyperammonemias and spontaneous protein aversion. Subnormal growth is common in spite of appropriate nutritional therapy. Growth hormone (GH) therapy promotes appetite, protein synthesis and accretion, but its possible growth-promoting effects and safety in patients with LPI are poorly known.

Metabolomics in angiotensin II-induced cardiac hypertrophy.

Angiotensin II (Ang II) induces mitochondrial dysfunction. We tested whether Ang II alters the "metabolomic" profile. We harvested hearts from 8-week-old double transgenic rats harboring human renin and angiotensinogen genes (dTGRs) and controls (Sprague-Dawley), all with or without Ang II type 1 receptor (valsartan) blockade.

Cow's milk allergy is associated with changes in urinary organic acid concentrations.

Cow's milk allergy (CMA) is the most common form of food allergy affecting 2.5% of children, but the diagnosis is often difficult. Both intestinal microbiota and barrier function seem to be disturbed in patients with food allergies, and administration of probiotics has been shown to normalize intestinal microbiota and alleviate symptoms.

Differential metabolic consequences of fumarate hydratase and respiratory chain defects.

Defects of the oxidative ATP production pathway lead to an amazing variety of disease phenotypes, ranging from childhood encephalomyopathies to hereditary tumor formation. A key enzyme of tricarboxylic cycle, fumarate hydratase (FH), is involved in encephalopathies, but also in leiomyoma formation, and occasionally also in various types of cancer. MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) and NARP (neuropathy ataxia retinitis pigmentosa) are progressive neurological disorders, caused by mitochondrial DNA mutations and respiratory chain (RC) deficiency.