Primary Hyperoxaluria Type 1 in Japan

Abstract

Background/Aims: Current status of primary hyperoxaluria (PH) has not been surveyed in Japan. Methods: Japanese patients with PH were reviewed in the published literature. Results: Fifty-nine patients were diagnosed as PH from 1962 to 2003. The median ages both at diagnosis and at the onset of initial symptoms were 17 (range: 0.02–63) and 13 (range: 0–58) years, respectively. Twenty-nine (49%) patients were older than 20 years at diagnosis, among whom 26 (90%) already presented end-stage renal failure (ESRF) or soon evolved into ESRF. Among 30 (51%) diagnosed as PH under 20 years old, only 13 (43%) were already in a terminal stage of renal insufficiency. Ten patients were diagnosed as PH1 by liver biopsy. We identified two types of enzymatic phenotypes in 3 of those patients examined. In 1 case, immunoreactive SPT/AGT protein level was very low due to accelerated proteolysis, while in other 2 cases, the immunoreactivity was detected on mitochondria due to mistargeting. Of 9 cases having been subjected to kidney transplantation at a median age of 20 years (range 7.3–40.0), it was only 2 cases that were reported to be successful, while the median survival time of the kidney grafts being 1.4 years (range 0–7). Of 4 patients having undergone combined liver/kidney transplantations (at the ages of 1.3, 1.4, 9 and 41 years, respectively), the surgery was successful in 3 cases; in the remaining one case, however, rejection required removal of the transplanted kidney was observed. The overall survival ratio of all the 59 PH cases accounted for 77, 71 and 55% at 5, 10 and 20 years, respectively. Conclusion: Assuming that the majority of the 59 patients with PH reported was classified as PH1, it is postulated that morbidity of violent infantile PH1 in Japan might be less than those in the USA and Europe, and symptoms of elderly Japanese PH1 patients seem to be milder than those of Western patients. Establishment of an early detection system of PH1 and more popular application of combined liver/kidney transplantation deserve further study.

Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1

“…However, our results were similar to the study of Takamaya et al. (), who reported a frequency of 49% of 59 Japanese patients being over 20 years of age at the time of diagnosis. Also, our results confirm the high prevalence of ESRD at the time of diagnosis and extra‐renal symptoms in the entire population, approximately in 50% of adult‐diagnosed patients.…”

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria

“…6,25,[41][42][43] PH1 was the most severe PH type ( Figure 2, Table 2), with a median age of first symptoms (5.2 years) and a cumulative renal survival (76%, 43%, and 12% at 20 years, 40 years, and 60 years, respectively) similar to that reported in the literature. 1,2,5,18,25 Further, although elevated urinary excretion of glycolate suggested PH1, the range (6.0-1183.0 mg/g creatinine) overlapped with other PH types and NMD patients b Normal values may be higher in children from birth to 5 years of age.…”

The primary hyperoxalurias

“…Whether there are regional variations in disease expression remains to be determined, though early observations are of interest [26]. A recent Japanese survey of 59 patients documented a milder course (30 % with onset of symptoms after age 25 years) than was observed in an historical European cohort [27, 28]. A substantial proportion of patients (11– 30 %, Japan up to 75%) are diagnosed late with symptoms of advanced renal failure or early kidney graft failure.…”