Hyperpipecolic acidaemia: a diagnostic tool for peroxisomal disorders

Peduto, Antonella; Baumgartner, Matthias R.; Verhoeven, Nanda M.; Rabier, Daniel; Spada, Marco; Nassogne, Marie‐Cécile; Poll-Thé, Bwee Tien; Bonetti, G; Jakobs, Cornelis; Saudubray, Jean Marie

doi:10.1016/j.ymgme.2004.04.010

Cited by 50 publications

(35 citation statements)

References 57 publications

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“…AASA elevations while on pyridoxine varied from 2.5-to 39-fold in plasma and from 1.6-to 62-fold in urine. While AASA is a pathognomonic marker of defects in the antiquitin gene, PA has the disadvantage of also being elevated secondarily in liver disease and in peroxisomal defects like Zellweger syndrome [Peduto et al, 2004]. In contrast, AASA is the primary substrate of the affected enzyme, aaminoadipic semialdehyde dehydrogenase, and remains more markedly elevated than PA in plasma and urine in all patients [Kelley, 1991].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene

et al. 2006

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“…The elevation in pipecolic acid was critical to determining that this patient had an assembly defect rather than an isolated defect in peroxisomal b-oxidation. Thus, although pipecolic acidaemia can be associated with nonspecific liver disease, diet, or the isolated defect of alphaaminoadipic semialdehyde dehydrogenase deficiency, it is a very useful marker when measured in conjunction with other peroxisomal biomarkers (Baas et al 2002;Mills et al 2006;Peduto et al 2004). Rarely, elevations in plasma pipecolic acid have been reported in patients with the peroxisomal disorders rhizomelic chondrodysplasia punctata and adult Refsum disease, although the basis of this is not understood (Peduto et al 2004).…”

Section: P L C T L C L E E R R H S Rat P L C T L C L E E R R H S Chicmentioning

confidence: 99%

A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts

Steinberg

Snowden

Braverman

et al. 2008

J of Inher Metab Disea

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Zellweger spectrum disorders (ZSD) are diagnosed by biochemical assay in blood, urine and cultured fibroblasts and PEX gene mutation identification. In most cases studies in fibroblasts corroborate results obtained in body fluids. In 1996 Clayton and colleagues described a 10-year old girl with evidence of a peroxisome disorder, based on elevated bile acid metabolites and phytanate. At the time it was not possible to distinguish whether she had a ZSD or a single peroxisomal protein defect. Studies in our laboratory showed that she also had elevated plasma pipecolate, supporting the former diagnosis. Despite the abnormal metabolites detected in blood (phytanate, bile acid intermediates and pipecolate), analysis of multiple peroxisomal pathways in fibroblasts yielded normal results. In addition, she had a milder clinical phenotype than usually associated with ZSD. Since complementation analysis to determine the gene defect was not possible, we screened this patient following the PEX Gene Screen algorithm (PGS). The PGS provides a template for sequencing PEX gene exons independent of complementation analysis. Two mutations in PEX10 were identified, a frameshift mutation inherited from her father and a de novo missense mutation in a conserved functional domain on the other allele. This case highlights that molecular analysis may be essential to the diagnosis of patients at the milder end of the ZSD spectrum. Furthermore, it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver.

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“…4 However, it is important to recognize that PA also can be elevated secondary to liver disease and in peroxisomal disorders. 17 Similarly, elevated AASA is not specific and can be associated with isolated sulfite oxidase deficiency and the related condition, molybdenum cofactor deficiency. 18 CSF monoamine metabolite analysis shows specific peaks (of yet undetermined compounds) and elevated AASA specific to PDE.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy

et al. 2015

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Pyridoxine-dependent epilepsy is a rare, autosomal recessive, treatable cause of neonatal seizures. Genetic testing can confirm mutations in the ALDH7A1 gene, which encodes antiquitin. To avoid delays in initiating treatment while awaiting confirmatory genetic testing, it is recommended that all neonates with unexplained seizures should receive trial of intravenous (IV) pyridoxine to assess for responsiveness. However, oral pyridoxine is not commonly continued in the absence of the typical EEG changes. Two cases are presented that highlight the potential inadequacy of this single-step approach. One neonate ultimately diagnosed with pyridoxine-dependent seizures had no EEG changes after administration of IV pyridoxine. In contrast, another neonate who did not have this diagnosis had profound EEG changes after pyridoxine administration. We present 2 cases that highlight the difficulties in using initial EEG response to IV pyridoxine in establishing a diagnosis of pyridoxine-dependent seizures in the neonate. Given the availability of biochemical markers and gene testing, we suggest that oral pyridoxine treatment should be continued until biochemical and/or genetic testing has confirmed the presence or absence of pyridoxine-dependent epilepsy.

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Hyperpipecolic acidaemia: a diagnostic tool for peroxisomal disorders

Cited by 50 publications

References 57 publications

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene

A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts

Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy

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