Asymptomatic a‐ketoadipic aciduria detected during a pilot study of neonatal urine screening

Peng, H; Shinka, Toshikatsu; Inoue, Yoshito; Mitsubuchi, Hiroshi; Ishimatsu, Junji; Yoshino, Makoto; Kuhara, Tomiko

doi:10.1111/j.1651-2227.1999.tb00070.x

Cited by 7 publications

(5 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In human, elevated levels of 2-aminoadipate has been found in infants with metabolic disease, which is caused by a defect in the oxidative decarboxylation of 2-oxoadipate, a catabolic intermediate of lysine, tryptophan, and hydroxylysine . It has been previously reported that 5 out of 7 children with an elevated level of 2-aminoadipate presented with psychomotor retardation . Additionally, 2-aminoadipate has been shown to relate to neurological disorders, such as seizures and convulsions .…”

Section: Discussionmentioning

confidence: 99%

“…44 It has been previously reported that 5 out of 7 children with an elevated level of 2-aminoadipate presented with psychomotor retardation. 45 Additionally, 2-aminoadipate has been shown to relate to neurological disorders, such as seizures and convulsions. Likewise, this metabolite has also been found in increased concentrations in the urine of experimental animals treated with the steatotic hepatotoxin hydrazine.…”

Section: Discussionmentioning

confidence: 99%

“…44 It has been previously reported that 5 out of 7 children with an elevated level of 2-aminoadipate presented with psychomotor retardation. 45 Additionally, 2-aminoadipate has been shown to relate to neurological disorders, such as seizures and convulsions. americanus-infected (pink solid squares) and uninfected control hamsters (black solid diamonds).…”

Section: Wang Et Almentioning

confidence: 99%

See 2 more Smart Citations

Systems Metabolic Effects of a Necator americanus Infection in Syrian Hamster

et al. 2009

View full text Add to dashboard Cite

Hookworms (Ancylostoma duodenale and Necator americanus) are blood-feeding intestinal nematodes that infect ∼700 million people worldwide. To further our understanding of the systems metabolic response of the mammalian host to hookworm infection, we employed a metabolic profiling strategy involving the combination of 1 H NMR spectroscopic analysis of urine and serum and multivariate data analysis techniques to investigate the biochemical consequences of a N. americanus infection in the hamster. The infection was characterized by altered energy metabolism, consistent with hookworminduced anemia. Additionally, disturbance of gut microbiotal activity was associated with a N. americanus infection, manifested in the alterations of microbial-mammalian cometabolites, including phenylacetylglycine, p-cresol glucuronide, 4-hydroxy-3-methyl-phenylpropionic acid, hippurate, 4-hydroxyphenylactate, and dimethylamine. The correlation between worm burden and metabolite concentrations also reflected a changed energy metabolism and gut microbial state. Furthermore, elevated levels of urinary 2-aminoadipate was a characteristic feature of the infection, which may be associated with the documented neurological consequences of hookworm infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…44 It has been previously reported that 5 out of 7 children with an elevated level of 2-aminoadipate presented with psychomotor retardation. 45 Additionally, 2-aminoadipate has been shown to relate to neurological disorders, such as seizures and convulsions. americanus-infected (pink solid squares) and uninfected control hamsters (black solid diamonds).…”

Section: Wang Et Almentioning

confidence: 99%

See 1 more Smart Citation

Systems Metabolic Effects of a Necator americanus Infection in Syrian Hamster

et al. 2009

View full text Add to dashboard Cite

show abstract

“…An additional search was performed in Pubmed with the search terms: “metabolite name” AND urin* AND concentration AND (newborn* OR neonate* OR infant*) AND (NICU or “neonatal intensive care unit, accessed on 30 May 2023). The concentration values (when available) were included in the Supplementary Table S2 [ 6 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Notably for 37 metabolites measured in this study, there were no existing literature reports on urinary concentration levels (quantitative results) in newborns or infants under the selected criteria.…”

Section: Resultsmentioning

confidence: 99%

“…The following supporting information can be downloaded at: , Table S1: Compound classification; Table S2: Urinary concentration values for NICU newborns and reference values found in HMDB ( , accessed on 30 May 2023) and Pubmed ( , accessed on 30 May 2023) [ 6 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]; Table S3: Perinatal characteristics and maternal history of newborns diagnosed with BPD and non-BPD newborns; Table S4: Fold Changes (FC) for Healthy vs. NICU newborns. Table S5: Pathway analysis: healthy vs. NICU newborns; Figure S1: Volcano plot comparison of BPD newborns (cesarean vs. va, c/v).…”

mentioning

confidence: 99%

The Urinary Metabolome of Newborns with Perinatal Complications

López-Hernández,

Lima-Rogel,

Mandal

et al. 2024

Metabolites

View full text Add to dashboard Cite

Maternal pathological conditions such as infections and chronic diseases, along with unexpected events during labor, can lead to life-threatening perinatal outcomes. These outcomes can have irreversible consequences throughout an individual’s entire life. Urinary metabolomics can provide valuable insights into early physiological adaptations in healthy newborns, as well as metabolic disturbances in premature infants or infants with birth complications. In the present study, we measured 180 metabolites and metabolite ratios in the urine of 13 healthy (hospital-discharged) and 38 critically ill newborns (admitted to the neonatal intensive care unit (NICU)). We used an in-house-developed targeted tandem mass spectrometry (MS/MS)-based metabolomic assay (TMIC Mega) combining liquid chromatography (LC-MS/MS) and flow injection analysis (FIA-MS/MS) to quantitatively analyze up to 26 classes of compounds. Average urinary concentrations (and ranges) for 167 different metabolites from 38 critically ill NICU newborns during their first 24 h of life were determined. Similar sets of urinary values were determined for the 13 healthy newborns. These reference data have been uploaded to the Human Metabolome Database. Urinary concentrations and ranges of 37 metabolites are reported for the first time for newborns. Significant differences were found in the urinary levels of 44 metabolites between healthy newborns and those admitted at the NICU. Metabolites such as acylcarnitines, amino acids and derivatives, biogenic amines, sugars, and organic acids are dysregulated in newborns with bronchopulmonary dysplasia (BPD), asphyxia, or newborns exposed to SARS-CoV-2 during the intrauterine period. Urine can serve as a valuable source of information for understanding metabolic alterations associated with life-threatening perinatal outcomes.

show abstract

Lipoic acid biosynthesis defects

Mayr

Feichtinger

Tort

et al. 2014

J of Inher Metab Disea

204

196

View full text Add to dashboard Cite

Lipoate is a covalently bound cofactor essential for five redox reactions in humans: in four 2-oxoacid dehydrogenases and the glycine cleavage system (GCS). Two enzymes are from the energy metabolism, α-ketoglutarate dehydrogenase and pyruvate dehydrogenase; and three are from the amino acid metabolism, branched-chain ketoacid dehydrogenase, 2-oxoadipate dehydrogenase, and the GCS. All these enzymes consist of multiple subunits and share a similar architecture. Lipoate synthesis in mitochondria involves mitochondrial fatty acid synthesis up to octanoyl-acyl-carrier protein; and three lipoate-specific steps, including octanoic acid transfer to glycine cleavage H protein by lipoyl(octanoyl) transferase 2 (putative) (LIPT2), lipoate synthesis by lipoic acid synthetase (LIAS), and lipoate transfer by lipoyltransferase 1 (LIPT1), which is necessary to lipoylate the E2 subunits of the 2-oxoacid dehydrogenases. The reduced form dihydrolipoate is reactivated by dihydrolipoyl dehydrogenase (DLD). Mutations in LIAS have been identified that result in a variant form of nonketotic hyperglycinemia with early-onset convulsions combined with a defect in mitochondrial energy metabolism with encephalopathy and cardiomyopathy. LIPT1 deficiency spares the GCS, and resulted in a combined 2-oxoacid dehydrogenase deficiency and early death in one patient and in a less severely affected individual with a Leigh-like phenotype. As LIAS is an iron-sulphur-cluster-dependent enzyme, a number of recently identified defects in mitochondrial iron-sulphur cluster synthesis, including NFU1, BOLA3, IBA57, GLRX5 presented with deficiency of LIAS and a LIAS-like phenotype. As in DLD deficiency, a broader clinical spectrum can be anticipated for lipoate synthesis defects depending on which of the affected enzymes is most rate limiting.

show abstract

Asymptomatic a‐ketoadipic aciduria detected during a pilot study of neonatal urine screening

Cited by 7 publications

References 14 publications

Systems Metabolic Effects of a Necator americanus Infection in Syrian Hamster

Systems Metabolic Effects of a Necator americanus Infection in Syrian Hamster

The Urinary Metabolome of Newborns with Perinatal Complications

Lipoic acid biosynthesis defects

Contact Info

Product

Resources

About