부산대학교 도서관

Objectives To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout. Methods We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d- lactate dosages were analysed using ELISA. Results We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C>T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P  = 0.02), lower fractional clearance of urate (P  = 0.002), and higher levels of d -lactate in blood (P  = 0.04) and urine (P  = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d -lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C>T, p.(Thr251Met)]. Conclusion Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d -lactate levels in the blood and/or urine. [ABSTRACT FROM AUTHOR]