Table 2.
Disorders of special interest presenting with urolithiasis and/or nephrocalcinosis. For further information see other chapters of the teaching series on urolithiasis in childhood. MIM Mendelian inheritance in man (catalogue no.), HPRT hypoxanthine-guanine-phosphoribosyl transferase, APRT adenine phosphoribosyltransferase, dRTA distal renal tubular acidosis, AD autosomal dominant, AR autosomal recessive, XLR, X linked recessive, LMW low molecular weight, CRF chronic renal failure
| MIM | Locus, gene | Inheritance | Gene product | Phenotype | |
|---|---|---|---|---|---|
| Hypercalciuria-induced urolithiasis/nephrocalcinosis | |||||
| Autosomal dominant hypocalcemic hypercalciuria | 146200; 601199 | 3q13.3- q21, CASR | AD | CASR | Hypercalciuria |
| Hypocalcemia | |||||
| CRF | |||||
| Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) | 248250; 603959 | 3q27, 1p34.2, CLDN16, CLDN 19 | AR | Paracellin 1, (Claudin 16, 19) | Hypercalciuria, hypercalcemia, hypomagnesemia, dRTA, CRF, hypermagnesuria, polyuria, tetany seizures |
| Dent’s disease, (Dent 1) | 300009; 310468; 300008 | Xp11.22, CLCN5 | XLR | CLC-5 | Hypercalciuria, renal phosphate leak (variable), LMW proteinuria, hypophosphatemia (variable) |
| Lowe syndrome, (Dent 2) | 309000 | Xq.25-26, OCRL1 | XLR | OCRL1 protein | Hypercalciuria, megalin deficiency, phosphate leak, Fanconi syndrome |
| Bartter’s syndrome type 1 | 600839 | 15q15-q21.1, NKCC2 | AR | SLC12A1 | Salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria, nephrocalcinosis |
| Bartter’s syndrome type 2 | 600359 | 11q24, ROMK | AR | KCNJ1 | Salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria, nephrocalcinosis |
| Infantile Bartter’s syndrome with sensorineural deafness | 602522; 606412; 602024; 602023 | 1p31, 1p36, BSND CLCNKB | AR | Salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria, nephrocalcinosis | |
| Williams–Beuren syndrome | 194050; 130160; 601329; 600404 | contiguous gene deletion syndrome 7q11.23, ELN, LIMK1, RFC2 | AD | Elastin, LIM-kinase 1 | Hypercalcemia, hypercalciuria, mental retardation ‘happy party manner’, aortic stenosis, ‘Elfin-faces’, nephrocalcinosis |
| Nephrolithiasis and osteoporosis associated with hypophosphatemia due to mutation in the type 2 sodium phosphate co-transporter | 182309 | 5q.35 | Unknown | NPTZa | Renal phosphate leak, hypercalciuria, osteoporosis, ↑ 1,25 dihydroxy-vitamin D |
| Hyperoxaluria-induced urolithiasis/nephrocalcinosis | |||||
| Primary hyperoxaluria, type I | 259900; 604285 | 2q.37.3, AGXT | AR | AGT | Hyperoxaluria, hyperglycolic aciduria, CRF, systemic oxalosis |
| Primary hyperoxaluria, type II | 260000; 604296 | 9q.11, GRHPR | AR | GR/HPR | Hyperoxaluria, L-gylceric aciduria, CRF |
| Cystinuria and urolithiasis | |||||
| Cystinuria type A | 104614 | 2p q.16.3, SLC3A1 | AR | r BAT | Elevated urinary excretion of cystine (and other dibasic amino acids) |
| Urine microscopy: hexagonal cystine crystals, recurrent urolithiasis, (CRF) | |||||
| Cystinuria type B | 604144 | 19 q.13.1/SLC7A9 | Inc AR | B α + AT | Elevated urinary excretion of cystine (and other dibasic amino acids) |
| Urine microscopy: hexagonal cystine crystals, recurrent urolithiasis, (CRF) | |||||
| Cystinuria type A/B | 220100 | SLC3A1/SLC7A1 | |||
| Purine/pyrimidine-induced urolithiasis/nephrocalcinosis | |||||
| Lesch–Nyhan syndrome | 300322 | Xq26, HPRT | XLR | HPRT | Hyperuricosuria, gout, automutilation, recurrent urolithiasis |
| Partial HPRT deficiency | 308000 | Xq.26–27.2, HPRT | XLR | HPRT | Hyperuricosuria |
| Glycogenosis type 1a | 232200 | 17q.21, G6PC | AR | Glucose-6-phosphatase | Hyperuricosuria |
| Glycogenosis type 1b | 232220 | 11q.23, SLC37A4 | AR | Transporter | Hyperuricosuria |
| Phosphoribosylphosphate synthetase 1 superactivity | 311850 | Xq21, PRPS1 | XL | Hyperuricosuria | |
| APRT deficiency | 102600 | 16q.24.3, APRT | AR | APRT | 2,8 Dihydroxy-adeninuria, recurrent crystalluria (round + brown), urolithiasis (radiolucent), rarely renal failure from crystal nephropathy |
| Xanthinuria (classical) | 278300 | 2p.22, XDH | AR | Xanthine oxydoreductase or dehydrogenase | Xanthinuria, hypouricemia |
| Distal renal tubular acidosis | |||||
| Renal tubular acidosis autosomal dominant | 179800; 109270 | 17q.21–q.22, SLC4A1, AE1 | AD | AE1 | Hypocitric aciduria, hypercalciuria, hypokalemia, osteomalacia |
| Autosomal recessive dRTA with hearing loss | 267300; 192132 | 2cen-q13, ATP6B1 | AR | B1 | Hypercalciuria, hypocitric aciduria, hypokalemia, rickets, hearing loss |
| Autosomal recessive dRTA | 602722; 605239 | 7q.33-34, SLC4A1 | AR | A4 | Hypercalciuria, hypocitric aciduria, hypokalemia |