Universität zu Köln

Mandrile, Giorgia, Beck, Bodo, Acquaviva, Cecile, Rumsby, Gill, Deesker, Lisa, Garrelfs, Sander, Gupta, Asheeta, Bacchetta, Justine and Groothoff, Jaap (2023). Genetic assessment in primary hyperoxaluria: why it matters. Pediatr. Nephrol., 38 (3). S. 625 - 635. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

Accurate diagnosis of primary hyperoxaluria (PH) has important therapeutic consequences. Since biochemical assessment can be unreliable, genetic testing is a crucial diagnostic tool for patients with PH to define the disease type. Patients with PH type 1 (PH1) have a worse prognosis than those with other PH types, despite the same extent of oxalate excretion. The relation between genotype and clinical phenotype in PH1 is extremely heterogeneous with respect to age of first symptoms and development of kidney failure. Some mutations are significantly linked to pyridoxine-sensitivity in PH1, such as homozygosity for p.G170R and p.F152I combined with a common polymorphism. Although patients with these mutations display on average better outcomes, they may also present with CKD stage 5 in infancy. In vitro studies suggest pyridoxine-sensitivity for some other mutations, but confirmatory clinical data are lacking (p.G47R, p.G161R, p.I56N/major allele) or scarce (p.I244T). These studies also suggest that other vitamin B6 derivatives than pyridoxine may be more effective and should be a focus for clinical testing. PH patients displaying the same mutation, even within one family, may have completely different clinical outcomes. This discordance may be caused by environmental or genetic factors that are unrelated to the effect of the causative mutation(s). No relation between genotype and clinical or biochemical phenotypes have been found so far in PH types 2 and 3. This manuscript reviews the current knowledge on the genetic background of the three types of primary hyperoxaluria and its impact on clinical management, including prenatal diagnosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mandrile, Giorgia UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Bodo UNSPECIFIED UNSPECIFIED UNSPECIFIED Acquaviva, Cecile UNSPECIFIED UNSPECIFIED UNSPECIFIED Rumsby, Gill UNSPECIFIED UNSPECIFIED UNSPECIFIED Deesker, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Garrelfs, Sander UNSPECIFIED UNSPECIFIED UNSPECIFIED Gupta, Asheeta UNSPECIFIED UNSPECIFIED UNSPECIFIED Bacchetta, Justine UNSPECIFIED UNSPECIFIED UNSPECIFIED Groothoff, Jaap UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687851
DOI:	10.1007/s00467-022-05613-2
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	38
Number:	3
Page Range:	S. 625 - 635
Date:	2023
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-198X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALANINE-GLYOXYLATE AMINOTRANSFERASE; GENOTYPE-PHENOTYPE CORRELATION; TYPE-1 PRIMARY HYPEROXALURIA; ALANINEGLYOXYLATE AMINOTRANSFERASE; AGXT MUTATION; CLINICAL HETEROGENEITY; SINGLE-CENTER; PYRIDOXINE; AGGREGATION; DISORDERS Multiple languages Pediatrics; Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68785