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Sarcosinemia is an autosomal recessive metabolic disorder characterized by elevated sarcosine due to deficient conversion to glycine by the mitochondrial enzyme SARDH. In a candidate gene study of six families (PMID:22825317), four distinct SARDH alleles were identified in three probands (PMID:22825317) and uniparental disomy in one additional case (PMID:22825317), with variant spectrum including two missense (p.Pro287Leu, p.Val71Phe) and two truncating alleles (p.Arg514Ter, p.Arg723Ter). No SARDH mutations were found in two other affected individuals, indicating genetic heterogeneity. Biallelic loss-of-function supports a haploinsufficiency mechanism, yet direct patient-derived functional assays are lacking. Overall, limited clinical validity and genetic evidence support the SARDH–sarcosinemia association. Key take-home: Biallelic SARDH inactivation serves as a molecular diagnostic marker for sarcosinemia screening.
Gene–Disease AssociationLimitedFour probands with biallelic SARDH variants and one uniparental disomy in six families ([PMID:22825317]); no segregation beyond probands. Genetic EvidenceLimitedFour probands with biallelic SARDH variants across six families, variant spectrum includes two missense and two truncating alleles ([PMID:22825317]). Functional EvidenceLimitedEnzymatic role of SARDH supports loss-of-function mechanism; no patient-derived functional validation. |