An integrated multi-omics approach allowed ultra-rapid diagnosis of a deep intronic pathogenic variant in PDHX and precision treatment in a neonate critically ill with lactic acidosis.

The diagnosis of mitochondrial disorders is complex. Rapid whole genome sequencing is a first line test for critically ill neonates and infants allowing rapid diagnosis and treatment. Standard genomic technology and bioinformatic pipelines still have an incomplete diagnostic yield requiring complementary approaches.

Compensation for metabolic dietitians practicing in the United States: 2023 genetic metabolic dietitians international professional status survey.

Background: Genetic Metabolic Dietitians International (GMDI) conducted a professional status survey of metabolic dietitians working in the United States to describe job satisfaction and establish salary and compensation benchmarks specific to metabolic dietitians.

Methods: The survey was anonymously administered in a web-based format via REDCap between October and November 2023. Registered dietitians working with inborn errors of metabolism (IEM) were eligible to participate.

Dietary management for pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency, a follow-on from the international consortium guidelines.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a neurometabolic disorder in the lysine metabolism pathway. In 2014 and 2021, the International PDE consortium published consensus guidelines about diagnosis and management. In this follow-on, a literature review was performed and nutrition management was evaluated through an international dietary questionnaire with 40 respondents.

REVIEW: Practical strategies to maintain anabolism by intravenous nutritional management in children with inborn metabolic diseases.

One of the most vital elements of management for patients with inborn errors of intermediary metabolism is the promotion of anabolism, the state in which the body builds new components, and avoidance of catabolism, the state in which the body breaks down its own stores for energy. Anabolism is maintained through the provision of a sufficient supply of substrates for energy, as well as critical building blocks of essential amino acids, essential fatty acids, and vitamins for synthetic function and growth. Patients with metabolic diseases are at risk for decompensation during prolonged fasting, which often occurs during illnesses in which enteral intake is compromised.

Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor.

Neutropenia and neutrophil dysfunction cause serious infections and inflammatory bowel disease in glycogen storage disease type Ib (GSD-Ib). Our discovery that accumulating 1,5-anhydroglucitol-6-phosphate (1,5AG6P) caused neutropenia in a glucose-6-phosphatase 3 (G6PC3)-deficient mouse model and in 2 rare diseases (GSD-Ib and G6PC3 deficiency) led us to repurpose the widely used antidiabetic drug empagliflozin, an inhibitor of the renal glucose cotransporter sodium glucose cotransporter 2 (SGLT2). Off-label use of empagliflozin in 4 GSD-Ib patients with incomplete response to granulocyte colony-stimulating factor (GCSF) treatment decreased serum 1,5AG and neutrophil 1,5AG6P levels within 1 month.

Impact on Isoleucine and Valine Supplementation When Decreasing Use of Medical Food in the Nutritional Management of Methylmalonic Acidemia.

Background: Methylmalonic acidemia (MMA) is an autosomal recessive disorder treated with precursor-free medical food while limiting natural protein. This retrospective chart review was to determine if there was a relationship between medical food, valine (VAL) and/or isoleucine (ILE) supplementation, total protein intake, and plasma amino acid profiles. Methods A chart review, of patients aged 31 days or older with MMA treated with dietary intervention and supplementation of VAL and/or ILE and followed at the Children's Hospital Colorado Inherited Metabolic Diseases Clinic.

Neurodevelopmental Outcome and Treatment Efficacy of Benzoate and Dextromethorphan in Siblings with Attenuated Nonketotic Hyperglycinemia.

Objective: To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia.

Study Design: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity.

Triple therapy with pyridoxine, arginine supplementation and dietary lysine restriction in pyridoxine-dependent epilepsy: Neurodevelopmental outcome.

Pyridoxine-dependent epilepsy (PDE) is an epileptic encephalopathy characterized by response to pharmacologic doses of pyridoxine. PDE is caused by deficiency of α-aminoadipic semialdehyde dehydrogenase resulting in impaired lysine degradation and subsequent accumulation of α-aminoadipic semialdehyde. Despite adequate seizure control with pyridoxine monotherapy, 75% of individuals with PDE have significant developmental delay and intellectual disability.