IllnessNephrolithiasis, expanded panel; differential diagnosis

NGS +

{Sanger]

Nephrolithiasis is most likely to develop from age 40-60, but stones can occur at any age; 35-50% of patients develop additional stones later. Although there are many sorts of kidney stones, four main types are distinguished according to their composition. Up to 75% of all kidney stones consist primarily of calcium, e.g. due to hypercalciuria. In addition, the stones may consist of uric acid, cystine or phosphate salts. Genetic alterations can increase the risk of developing kidney stones, often in combination with a number of environmental and lifestyle factors. Most of the genes involved transmit cell signals or transport substances in and out of cells. Changes in these genes can alter the amount of critical substances in the cells, leading to an imbalance of minerals and compounds in the urine. This increases the likelihood of stone formation. Dispositions that increase the overall risk for kidney stones include obesity, type 2 diabetes, inflammatory bowel disease, gout, hyperparathyroidism, renal tubular acidosis and recurrent urinary tract infections. Overall, the risk of developing nephrolithiasis is higher in individuals with affected relatives than in the general population. Inheritance of kidney stone disease is usually multifactorial. In the rare cases of mendelian inheritance, all classical transmission patterns occur. Gene panels identify a causative variant in about 20% of nephrolithiasis patients in childhood and less than 12-15% in adulthood (up to nearly 30% before age 25). The obvious clinical diagnosis can never be excluded by a negative DNA test result.

References: https://jasn.asnjournals.org/content/28/3/748.short

https://jasn.asnjournals.org/content/jnephrol/26/3/543.full.pdf

• Adenine phosphoribosyltransferase deficiency (APRT)
• Allelic: Amelogenesis imperfecta, type IIA3 (WDR72)
• Arthrogryposis, renal dysfunction + cholestasis 1 (VPS33B)
• Arthrogryposis, renal dysfunction + cholestasis 2 (VIPAS39)
• Cystinuria (SLC3A1, SLC7A9)
• Dent disease 2 (OCRL)
• Dent syndrome (CLCN5)
• Distal renal tubular acidosis 1 (SLC4A1)
• Distal renal tubular acidosis 2 with progressive sensorineural hearing loss (ATP6V1B1)
• Distal renal tubular acidosis 3, with/-out sensorineural hearing loss (ATP6V0A4)
• Distal renal tubular acidosis 4 with hemolytic anemia (SLC4A1)
• Distal renal tubular acidosis [MONDO:0015827] (WDR72)
• Fanconi renotubular syndrome 2 (SLC34A1)
• Hypercalcemia, infantile, 1 (CYP24A1)
• Hypercalcemia, infantile, 2 (SLC34A1)
• Hyperglycinuria (SLC36A2)
• Hyperoxaluria, primary, type I (AGXT)
• Hyperoxaluria, primary, type II (GRHPR)
• Hyperoxaluria, primary, type III (HOGA1)
• Hyperuricemia, HRPT-related (HPRT1)
• Hypomagnesemia 5, renal, with ocular involvement (CLDN19)
• Hypophosphatemic rickets, XLD (PHEX)
• Iminoglycinuria, digenic (SLC36A2)
• Lesch-Nyhan syndrome (HPRT1)
• Nephrolithiasis type 1 (CLCN5)
• Nephrolithiasis/osteoporosis, hypophosphatemic, 1 (SLC34A1)
• Osteopetrosis, AR 3, with renal tubular acidosis (CA2)
• Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis (CLCN5)
• Xanthinuria, type I (XDH)
• Xanthinuria, type II (MOCOS)