One primary interest of the research community is the rapid detection of severe hereditary diseases that, if treated late or improperly, may lead to progressive impairment of renal function and end-stage renal failure. Such a dramatic evolution is usually due to late or erroneous diagnosis. It is all the more unfortunate since it might be prevented or substantially delated y an appropriate treatment, and since a stone episode most often reveals these diseases. This aspect is to be especially emphasized with regards to two hereditary diseases of particularly high detrimental consequences:

This inherited disease is the most severe of all stone diseases due to the permanent endogenous (from within the body) overproduction of oxalate which leads to massive hyperoxaluria, recurrent COM kidney stones and nephrocalcinosis (deposits of calcium salts within the renal tubules, the tubular epithelium, and/or the interstitium) with a parenchymal deposit of COM crystals (deposits that negatively impact kidney function), decline in GFR (Glomerular filtration rate= how well the kidneys are functioning), hyperoxalemia with systemic oxalosis (a potentially life-threatening condition that results from the progression of primary or enteric hyperoxaluria. Excess oxalate that cannot be eliminated by the kidneys begins to accumulate in tissue throughout the body, including the blood, bones, joints, skin, eyes, heart, and kidneys), and ultimately end-stage renal disease requiring a combined liver-kidney transplant.

Discovery of Type Ic kidney stones made of pure COM with an unexpected clear color instead of the usual dark color or common COM stones should immediately alert to the probability of Primary Hyperoxaluria Type 1 (PH1). Laboratory evaluation to achieve a definitive diagnosis [4,86] and early institution of conservative medical treatments is suggested. It starts by testing the effect of pharmacological doses of pyridoxine, which diverts glyoxylate metabolism and may substantially reduce endogenous oxalate production. 

This condition is due to mutations of the enzyme adenine phosphoribosyltransferase (APRT). It results in both the formation of stones made of 2,8-DHA and infiltration of the renal parenchyma (the functional tissue of an organ as distinguished from the connective and supporting tissue) by 2,8-DHA crystals leading to extensive interstitial fibrosis and ultimately to end-stage renal disease, requiring chronic dialysis and kidney transplant.

DHA-based stones are typically embossed and rough on the surface and beige to rust-brown in color. They are often confused with uric acid stones. Unfortunately, alkalization is ineffective in treating DHA stone as you can with uric acid stones, which is why proper analysis is so critical.