We investigated the recent trend in the onset age of and factors influencing gout in Japan. Three hundred and fifty-eight male gouty patients, who first visited our clinic between June 2016 and May 2017, were enrolled. The average age at the onset of gout confirmed from patient reports was 41.9 ±10.8 years, and patients in their 40s were the most common, accounting for 36.9%, with 33.8% in their 30s, 13.1% in their 50s, and 9.8% in their 20s or younger. Those in their 70s or older comprised only 1.4%. Obesity was a major factor in the onset of gout in younger people, especially in their teens, and drinking habits as a cause of obesity were observed in all ages except those in their teens, especially those in their 60s. Although there were many cases with the uric acid underexcretion type, the renal overload type was more common in those in their 60s than in other age groups. Based on environmental factors including nutritional and qualitative changes in dietary habits, gout episodes involving younger people in Japan, mainly in their 30s to 40s, have increased over the 20 years from 1965 to 1984. However, it is considered that the age at onset has not changed since then.

Adenine phosphoribosyltransferase (APRT) catalyzes the synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. APRT deficiency (APRTD) results in an inability to utilize adenine, which is oxidized by xanthine dehydrogenase via 8-hydroxyadenine to 2,8-dihydroxyadenine. 2,8-Dihydroxyadenine is extremely insoluble, and its accumulation in the kidney results in crystalluria and the formation of urinary stones. Recently, a new approach for early diagnosis is expected worldwide, because of the increased recognition of delayed diagnosis. However, no specific approach has been proposed.

GC/MS-based metabolomics have been expected to facilitate the rapid, sensitive, and cost-effective chemical diagnosis of APRTD since 1997. We examined spot urine from four patients: 47 - and 61-year-old female siblings whose other sibling had died after 30 years of dialysis, a 66-year-old male with worsening kidney function, and a 29-year-old male with renal failure followed by kidney transplantation but with numerous crystals observed on post-operative day 3.

Within 1-2 days after sample arrival, all were found to have APRTD, because z- scores for the biomarkers were 6.1-8.9. Subsequent mutation analysis revealed APRT*J/J for the female and APRT*Q0/Q0 for males. Xanthine oxidase inhibitor prevented secondary 2,8-dihydroxyadenine nephrolithiasis after kidney transplantation.

We propose to modify the current diagnostic guidelines as follows: GC/MS-based metabolomics should be recommended at the start of the diagnosis, and also be recognized as a confirmative diagnosis if sample preparation, GC/MS measurement, and data analysis are performed in specialized laboratories. APRTD, xanthinuria type I-III, oxalosis type I-III, HPRT severe deficiency and, cystinuria are screened simultaneously at a cost of 15,000 JPY in our laboratory.

We have reported that when a fish is immersed in fermented sake lees, some purines in the fish migrate from the fish side to the soaked side. In this study, to compare different fermented foods, we investigated changes in the purine composition and behavior of swordfish soaked in Saikyo miso. The swordfish was soaked in Saikyo miso for 1 and 3 days. Purines of foods were measured by two methods using high performance liquid chromatography (HPLC) developed in our laboratory. The total purine contents of swordfish and Saikyo-miso were 149.7 and 40.9 mg/100 g respectively. When swordfish was soaked in Saikyo miso for 3 days, hypoxanthine (HX)-related purine in the swordfish was significantly decreased. HX-related purine in Saikyo miso after soaking for 3 days was significantly increased.

As the results of free purine measurement, inosine monophosphate (IMP), inosine (Ino), and HX in raw swordfish were abundantly detected. When soaked in Saikyo miso, Ino in swordfish decreased and Ino in Saikyo miso increased. Furthermore, as a result of solid-liquid separation of Saikyo miso, purines were mainly present on the liquid side.

Therefore, it was shown that Saikyo-zuke reduced the amount of Ino, which is an HX type that is abundant in swordfish, and that most of it moved to the liquid side of Saikyo miso. This dish should be recommended in dietary therapy for patients with hyperuricemia and gout.

It is well-known that gout attacks are common from spring to summer, and causes include dehydration due to a high temperature and changes in dietary habits depending on the season, but this is not clear. In this area of Japan, temperature fluctuations from May to September 2019 were more intense than usual, and it was possible to observe the relationship between temperature changes and gout attacks in this short period, excluding the effects of dietary changes. In interviews, we asked questions on the onset time to 105 first-time patients (mean age: 48.2 years ± 12.5, median: 47 years old, all male patients) who visited our outpatient clinic with a gout attack from May 1st to September 30th, 2019. When compared with the temperature data in Kumamoto of the Japan Meteorological Agency (maximum temperature, minimum temperature, temperature difference), the highest temperature was lower in May compared with other months, but the average temperature difference was 11.4 °C, the largest during the period, and the number of patients was the highst. Moreover, the number of patients increased when the temperature fell once and then rose again. In May, the temperature rise and temperature difference were large, and it was considered that one of the reasons for the gouty attacks was that the body was not able to adapt to this temperature change. When the urine specific gravity was compared between the patients who had gouty attacks in May and August, it tended to be higher in the patients in May. For this reason, many people are concerned about drinking water in August when the temperature is high, but it is considered that the proportion of people who drink water actively in May when the temperature is still low may also be low. However, this survey consideres results from a limited time with a limited number of samples, and to clarify whether the same trend occur every year, it is necessary to conduct further studies.

Based on the results there were many gout attacks in the summer, but patient guidance was given in consideration of the fact that many gout attacks appear from the transition of the season such as early summer, and the source/volume of drinking water should be kept in mind from that time. Hopefully, more detailed patient guidance will be possible by carrying out such studies.

Lifestyle guidance is important for the treatment of gout and hyperuricemia. In nutritional guidance, it is necessary to understand the actual lifestyle habits of patients that should be improved most, to evaluate the effects of lifestyle habit improvement, and then to provide lifestyle guidance tailored to every patient.

Thus, we intended to produce a check sheet that can be used to easily examine the intake and frequency of both dietary purine and alcohol in hyperuricemic patients. We also intended to provide useful information to patients on their lifestyle habit improvement. In order to present recommended meals, questions in the check sheet were divided into two food groups: Foods to eat less of, and Foods to eat more of. We created two types of check sheets: "Dietary questionnaire on serum uric acid level" for questions, and "Advice lists for better dietary habits" for feedback, to avoid patients’ answers becoming learned. In order to allow the dietitian to roughly estimate the amount of dietary purine during the limited time of nutrition instructions, we created: "Amount of purines in representative dishes using meat or fish" and "Amount of purines (median and average) in meat and fish". Additionally, as a visual pamphlet for patients, we created: "Quantity of recommended daily ingredients weighed by hands with purine amounts".