title: Recurrent EIARF and PRES with severe renal hypouricemia by compound heterozygous SLC2A9 mutation.
abstract: Renal hypouricemia (RHU) is a hereditary disease that predisposes affected people to exercise-induced acute renal failure (EIARF). In most patients with RHU, the disorder is caused by loss-of-function mutations in SLC22A12 (solute carrier family 22, member 12), which encodes urate transporter 1 (URAT1). Patients with RHU without any mutations in the URAT1 gene were recently found to have a mutation in the glucose transporter 9 (GLUT9) gene (SLC2A9 [solute carrier family 2, member 9]). Central nervous system complications seem to be rare in patients with RHU with SLC22A12 mutations. Here, we report the case of a girl with severe RHU (serum urate: 5.9 μmol/L [0.1 mg/dL]) associated with recurrent EIARF in whom the disease was caused by a compound heterozygous mutation in SLC2A9, a nonsense mutation in the paternal allele (p.G207X in exon 7), and a large duplication (c.1-2981_1204+16502) in the maternal allele detected by reverse-transcription polymerase chain reaction (PCR), semiquantitative PCR, long PCR, and direct sequencing. The episodes of EIARF were complicated by posterior reversible encephalopathy syndrome (PRES), which suggested a relationship between PRES and GLUT9 or severe hypouricemia. This is the second report of mutations of both alleles of SLC2A9 that resulted in severe hypouricemia. Our findings indicate that even a nonsense mutation responsible for the heterozygous status of SLC2A9 did not cause severe hypouricemia, and they lend support to previous speculation that mutations of both SLC2A9 alleles cause severe hypouricemia. Our case shows that GLUT9, unlike URAT1, may play a specific role in exercise-induced PRES.
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama City, Wakayama, 641-8509, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shima
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nozu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D001480:Basal Ganglia Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D002524:Cerebellar Ataxia / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D012008:Recurrence; D015499:Renal Tubular Transport, Inborn Errors / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D012720:Severity of Illness Index; D014545:Urinary Calculi / Q000150:complications / Q000175:diagnosis / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D004247:DNA