Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia.

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.

[Introduction of an enzyme method for determining pyrophosphate in urine--a comparative study between patients with calculi and normal probands]. / Einführung einer enzymatischen Methode zur Bestimmung von Pyrophosphat im Urin--eine vergleichende Studie zwischen Steinbildnern und Gesunden.

Interest aroused towards pyrophosphate as a possible inhibitor in calcium oxalate and phosphate lithiasis. A procedure for the quantitative determination of pyrophosphate in urine suitable for use in clinical laboratories is described. The reproducibility of the method was assessed by within-run and between-run reproducibility studies and the accuracy of the method was obtained by determining the amount of pyrophosphate recovered in urine samples. The present study compares the pyrophosphate excretion and concentration between a control group and a calcium oxalate stone former group.

Biochemical and clinical effects of ethane-1-hydroxy-1,1-diphosphonate in calcium nephrolithiasis.

1. The short- and longer-term effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP), an inhibitor of crystal growth and potential preventive agent against urinary tract stones in man, have been studied. 2. Measurement of urinary excretion of EHDP was used to define the best dosage regimen. When 4.4 mmol of EHDP mmol of EHDP was given in four divided doses the murinary concentration of EHDP achieved was high enough (10-5 mol/1) to inhibit the crystallization of calcium crystals throughout the day. 3. Nine patients with recurrent calcium stones were given this dose of EHDP daily for 12 months and seven were then studied for a further 12 months under placebo. During treatment with EHDP, inhibitory activity in urine towards precipitation of calcium phosphate was restored from low values to greatly above normal. This could be accounted for by the inhibitory effect of EHDP itself, coupled with an increase in urinary inorganic pyrophosphate. After stopping EHDP the excretion of EHDP rapidly fell to undetectable levels but the excretion of pryophosphate remained elevated throughout the 12 months of placebo treatment. EHDP also induced a rise in plasma phosphate and an increase in the urinary excretion of oxalic acid and uric acid, but these changes were all fully reversible when EHDP was stopped. 4. The average rate of stone formation per patient per year decreased from 2.4 to 0.2 during treatment with EHDP and remained low during the following 24 months. However, the dose needed for this effect is known to affect bone turnover and mineralization.