A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal

Guanidinoacetate methyltransferase (GAMT) deficiency (MIM 601240), an autosomal recessive disorder of creatine biosynthesis, presents with mental retardation, extrapyramidal symptoms, autistic-like behavior and epilepsy. Other hallmarks are cerebral creatine deficiency, increased levels of guanidinoacetate in body fluids and mutations in the GAMT gene. Creatine supplementation partially restores cerebral creatine content. Worldwide, 29 patients have been identified and 15 different mutations have been reported in the GAMT gene. Ten out of these 29 patients are of Portuguese origin. Likely, a founder effect and a high carrier rate in Portugal exist, since in 17 out of the 20 Portuguese alleles the c.59G>C; p.Trp20Ser mutation was found. We investigated the carrier rate of the c.59G>C; p.Trp20Ser mutation in different regions of Portugal and confirmed the pathogenic nature of this missense mutation by transient transfections. Anonymous bloodspots (1002) were screened for the presence of the c.59G>C; p.Trp20Ser mutation by SNaPshot (Single Nucleotide Polymorphism Multiplex Kit). Eight carriers of c.59G>C; p.Trp20Ser were detected of which four are derived from the Archipelagos. This suggests that the carrier rate of the c.59G>C; p.Trp20Ser mutation is relatively high in these islands, as well as in other parts of Portugal. It also implies that newborn screening in these regions is warranted for this treatable disorder.