Abstract: SA-PO567
Rare Kidney Stone, Potassium Magnesium Pyrophosphate Pentahydrate Calculi, in Hypophosphatasia
Session Information
- Genetic Diseases: Diagnosis
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Gudura, Tariku Tadele, Cleveland Clinic, Cleveland, Ohio, United States
- Bartolomeo, Korey, Cleveland Clinic, Cleveland, Ohio, United States
- Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States
Group or Team Name
- Cleveland Clinic
Introduction
Hypophosphatasia(HPP) is a rare inherited disorder caused by loss of function mutation of ALPL that encodes
tissue nonspecific alkaline phosphate (TNSALP), characterized by impaired mineralization of bones and teeth in the
presence of low activity of serum and bone alkaline phosphatase. Kidney stones and nephrocalcinosis have been
reported in some cases and most of the stones are calcium containing. Late diagnosis of hypophosphatasia is not
uncommon. Here we present a case of a new diagnosis of hypophosphatasia for a 61 year old man after passing pure potassium
magnesium pyrophosphate pentahydrate stones, which is very rare.
Case Description
A 61-year-old with history of hypertension, diabetes, premature tooth loss, skeletal fractures and over 10 symptomatic nephrolithiasis since age 20 was sent for genetic evaluation. His most recent serum labs were relevant for creatinine 1.4 mg/dl, alkaline phosphatase (ALP) 6 U/L (40-130), bone specific ALP 1.6 µg/ml (6.5-20.1), vitamin B6 1,594.2 nmol/L (20-125), PTH 39 pg/ml (15-65) and 25-vitamin D 69.6 ng/ml (31-80). Calcium and phosphate were within normal lab limits. Urines studies were unremarkable with 24-hour urine protein 480 mg, presumed to be related to diabetic nephropathy or possible tubular injury from recurrent nephrolithiasis. His most recent stone analysis showed 100% potassium magnesium pyrophosphate pentahydrate (PMPP). Family history was significant for short stature and a mechanical fall related wrist fracture in his mother, and kidney stones and color blindness in his 2 nephews. Genetic test showed two heterozygous pathogenic variants, c.1240C>A (p. Leu414Met) and c.407G>A (p. Arg136His), in the ALPL gene confirming the diagnosis of HPP. Parental testing is pending to clarify its inheritance pattern. The patient was started on recombinant human TNSALP.
Discussion
Patients with HPP tend to have hypercalciuria with or without hypercalcemia from impaired bone uptake of calcium and phosphorus. This increases risk of nephrocalcinosis and calcium containing kidney stones. Our patient developed pure potassium magnesium pyrophosphate pentahydrate stone, which is very rare, and has not been reported in human beings. Its association with HPP is unclear and deserves further investigation.