A5001066679- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Folate and B Vitamins Research
- Diet and metabolism studies
- Neonatal Health and Biochemistry
- Genomics and Rare Diseases
- Biochemical and Molecular Research
- Amino Acid Enzymes and Metabolism
- Mass Spectrometry Techniques and Applications
- Cholesterol and Lipid Metabolism
- RNA modifications and cancer
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Muscle metabolism and nutrition
- Metabolomics and Mass Spectrometry Studies
- Educational Innovations and Challenges
- Peroxisome Proliferator-Activated Receptors
- Prenatal Screening and Diagnostics
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Sexual Differentiation and Disorders
- Psychology of Development and Education
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Kidney Stones and Urolithiasis Treatments
- Design Education and Practice
Murdoch Children's Research Institute
2015-2025
Victorian Clinical Genetics Services
2016-2025
Royal Children's Hospital
2011-2025
The University of Melbourne
2014-2024
University Medical Center Groningen
2021
Inserm
2021
Université de Tours
2021
Centre Hospitalier Universitaire de Tours
2021
University Surgical Associates
2019-2020
Ellen MacArthur Foundation
2015
Molybdenum cofactor deficiency (MoCD) is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused the functional loss of sulfite oxidase, 1 4 molybdenum-dependent enzymes. To date, no effective therapy available for MoCD, death in early infancy has been usual outcome. We report here case patient who was diagnosed with MoCD at age 6 days. Substitution purified cyclic pyranopterin monophosphate (cPMP) started on day 36 daily intravenous administration...
Tandem mass spectrometry is widely applied to routine newborn screening but there are no long-term studies of outcome. We studied the clinical outcome at six years age in Australia.In a cohort study, we analyzed 6 for patients detected by or diagnosis among >2 million infants born from 1994 1998 (1,017,800, all unscreened) and 2002 (461,500 screened, 533,400 recording intellectual physical condition, school placement, other medical problems, growth, treatment, diet, hospital admissions....
Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated Leigh-like disease. However, this diagnosis was excluded by HIBCH sequencing normal enzyme activity. In contrast to 3-hydroxyisobutyryl-carnitine children, suggesting deficiency short-chain enoyl-CoA hydratase (ECHS1 gene). This mitochondrial...
Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 have been identified humans with congenital malformations defined as deficiency disorder (CNDD). Here, we 13 further individuals predicted to be damaging, phenotypes ranging from multiple severe complete absence malformation. Enzymatic assessment variant...
Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period early childhood. We identified validated different CA5A alterations, including a homozygous missense mutation (c.697T>C) two siblings, splice site (c.555G>A) leading to skipping exon 4, 4 kb deletion 6. The deleterious nature c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity increased temperature...
<h3>Background</h3> Short-chain enoyl-CoA hydratase—ECHS1—catalyses many metabolic pathways, including mitochondrial short-chain fatty acid β-oxidation and branched-chain amino catabolic pathways; however, the products essential for diagnosis of ECHS1 deficiency have not yet been determined. The objective this report is to characterise a mild form its biochemically, determine candidate product that can be efficiently used neonatal diagnosis. <h3>Methods</h3> We conducted detailed clinical,...
Detection of abnormal metabolites in urine is important for the diagnosis many inborn errors metabolism (IEM). Rapid, comprehensive screening methods are needed.We used electrospray ionization tandem mass spectrometry positive- and negative-ion modes to detect selected urine. For positive-ion analysis, samples were dried butylated, whereas merely diluted with mobile phase. Analysis was by direct injection multiple reaction monitoring 32 positive mode (amino acids acylcarnitines) 30 negative...
Eukaryotic cells generate energy in the form of ATP, through a network mitochondrial complexes and electron carriers known as oxidative phosphorylation system. In mammals, complex I (CI) is largest component this system, comprising 45 different subunits encoded by nuclear DNA. Humans diagnosed with mutations gene NDUFS4, encoding DNA-encoded subunit CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, neurodegenerative disease onset infancy or early...
<h3>Importance</h3> Newborn screening for Angelman syndrome (AS), Prader-Willi (PWS), and chromosome 15 duplication (Dup15q) may lead to benefit from early diagnosis treatment. <h3>Objective</h3> To examine the feasibility of newborn these imprinting disorders at population scale. <h3>Design, Setting, Participants</h3> In this diagnostic study, validation data set first-tier<i>SNRPN</i>test, called methylation-specific quantitative melt analysis (MS-QMA), included 109 PWS, 48 AS, 9 Dup15q,...
We describe biochemical and clinical features of 11 subjects (ages, 1.2-84 years, nine females two males) with transient 5-oxoprolinuria (0.6-23.6 mol/mol creatinine, reference range <0.07). A variety conditions preceded the onset acidosis, all had taken acetaminophen (paracetamol), although in therapeutic amounts most subjects. Metabolic acidosis was documented subjects, an increased anion gap abnormal liver functions. 5-Oxoproline major urinary organic acid five whereas rest more complex...
Fasting is accompanied by a decrease in the availability of glucose for energy use peripheral tissues and, consequently, an increased reliance these on ketone bodies and fatty acids energy. The depends almost exclusively hepatic ketogenesis. Failure ketogenesis may occur patients with any defect enzymes associated mitochondrial oxidation acids.1 These defects are typically manifested hypoglycemia, which results from inadequate supply alternative substrate (ketones). Other clinical features...
Mitochondrial complex I (CI) deficiency is the most common mitochondrial enzyme defect in humans. Treatment of disorders currently inadequate, emphasizing need for experimental models. In humans, mutations NDUFS6 gene, encoding a CI subunit, cause severe and neonatal death. this study, we generated CI-deficient mouse model by knockdown Ndufs6 gene using gene-trap embryonic stem cell line. gt/gt mice have essentially complete knockout subunit heart, resulting marked deficiency. Small amounts...
Short‐chain enoyl‐CoA hydratase (SCEH or ECHS1) deficiency is a rare inborn error of metabolism caused by biallelic mutations in the gene ECHS1 (OMIM 602292). Clinical presentation includes infantile‐onset severe developmental delay, regression, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). Characteristic abnormal biochemical findings are secondary to dysfunction valine metabolism. We describe four patients from two consanguineous families (one...
Abstract Background: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the DHCR7 gene that result reduced cholesterol biosynthesis. The aim of study was to examine biochemical and clinical features SLOS context emerging evidence importance morphogenesis steroidogenesis. Methods: We retrospectively reviewed records 18 patients (including four fetuses) with confirmed documented their features. Results: Seven had branchial arch abnormalities, including...