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Introduction: Hyperuricemia and gout are classically attributed to disordered purine metabolism, reduced renal urate excretion, and acquired risk factors such as obesity, diet, or kidney disease. Rare monogenic forms, however, show that defects in intermediary metabolism may also disturb urate homeostasis. LDHD encodes d-lactate dehydrogenase, a key enzyme in d-lactate metabolism. Loss of function is thought to result in d-lactate accumulation with secondary enhancement of renal urate reabsorption, thereby linking intermediary metabolism to hyperuricemia. Such rare pediatric cases may uncover mechanisms that remain clinically relevant in atypical adult disease.

Results: An adolescent boy presented with recurrent acute monoarthritis, initially affecting the first metatarsophalangeal joint and later the right thumb. MRI demonstrated active arthritis without erosive damage. Persistent marked hyperuricemia (>600 µmol/L), despite absence of obesity, renal dysfunction, or other common secondary causes, prompted further metabolic and genetic evaluation. This identified compound-heterozygous LDHD variants c.561_562del (p.(Leu188Glnfs*56)) and c.1319C>T (p.(Thr440Met)), establishing the diagnosis of LDHD deficiency-associated hyperuricemia. Acute flares were controlled with NSAIDs and short-term glucocorticoids. Long-term therapy with allopurinol, titrated to 300 mg/day, together with colchicine prophylaxis (0.5 mg/day for 3 months), reduced serum urate to 465 µmol/L within five months and resulted in complete clinical remission with restoration of normal activity.

Conclusion: This case expands the metabolic framework of gout beyond purine turnover alone. LDHD deficiency highlights a mechanistically informative axis between d-lactate metabolism and renal urate handling. For rheumatologists, particularly in early-onset, lean, or otherwise atypical patients, hyperuricemia should prompt consideration of rare inherited metabolic causes. Monogenic juvenile gout may thus serve as a model disease for refining our understanding of hyperuricemia across the lifespan.

Disclosure of interest: none

References

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