Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification.
Recent developments in the genetics and physiology of cystinuria do not support the traditional classification, which is based on the excretion of cystine and dibasic amino acids in obligate heterozygotes. Mutations of only two genes (SLC3A1 and SLC7A9), identified by the International Cystinuria Consortium (ICC), have been found to be responsible for all three types of the disease. The ICC set up a multinational database and collected genetic and clinical data from 224 patients affected by cystinuria, 125 with full genotype definition. Amino acid urinary excretion patterns of 189 heterozygotes with genetic definition and of 83 healthy controls were also included. All SLC3A1 carriers and 14% of SLC7A9 carriers showed a normal amino acid urinary pattern (i.e., type I phenotype). The rest of the SLC7A9 carriers showed phenotype non-I (type III, 80.5%; type II, 5.5%). This makes the traditional classification imprecise. A new classification is needed: type A, due to two mutations of SLC3A1 (rBAT) on chromosome 2 (45.2% in our database); type B, due to two mutations of SLC7A9 on chromosome 19 (53.2% in this series); and a possible third type, AB (1.6%), with one mutation on each of the above-mentioned genes. Clinical data show that cystinuria is more severe in males than in females. The two types of cystinuria (A and B) had a similar outcome in this retrospective study, but the effect of the treatment could not be analyzed. Stone events do not correlate with amino acid urinary excretion. Renal function was clearly impaired in 17% of the patients.
Dello Strologo
Luca
L
Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy. dellostrologo@opbg.net
Pras
Elon
E
Pontesilli
Claudia
C
Beccia
Ercole
E
Ricci-Barbini
Vittorino
V
de Sanctis
Luisa
L
Ponzone
Alberto
A
Gallucci
Michele
M
Bisceglia
Luigi
L
Zelante
Leopoldo
L
Jimenez-Vidal
Maite
M
Font
Mariona
M
Zorzano
Antonio
A
Rousaud
Ferran
F
Nunes
Virginia
V
Gasparini
Paolo
P
Palacín
Manuel
M
Rizzoni
Gianfranco
G
D000293:Adolescent; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids / Q000652:urine; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D003555:Cystinuria / Q000145:classification* / Q000235:genetics* / Q000652:urine; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C499489:SLC7A9 protein, human