**1. Introduction**

Gout is the clinical manifestation of hyperuricemia which is triggered by urate precipitation (deposition of monosodium urate crystals) in the synovial fluid of joints and other tissues [1,2]. The disease is primarily associated with severe arthropathy, which manifests mainly in the metatarsophalangeal joints (podagra), but also in other joints of the foot, ankles, knee, wrist, fingers, and elbows [3]. In the pathogenesis of the disease, urate deposits promote inflammatory responses in the synovial membrane (synovitis) and thus arthritis characterized by sudden, severe attacks of pain, swelling, redness, and tenderness in the affected joints. Depending on the course of the disease, the symptoms of gout can occur both as acute episodic flares (gout attacks) and persist chronically and, if left untreated, can lead to irreversible deformations and impaired mobility of the affected joints [3]. In addition, gout nephropathy, a form of chronic tubulointerstitial nephritis, induced by the deposition of urate precipitates in the distal collecting ducts and the medullary interstitium may cause progressive chronic kidney disease [4]. Furthermore, gout and hyperuricemia have been associated with a subset of comorbidities including metabolic syndrome, diabetes, hypertension as well as cardiovascular and cerebrovascular disease [5–13]. In most patients, the onset of gout occurs after the age of 60, with the incidence being about three times higher in men than in women [14]. However, a significant proportion of patients develop primary hyperuricemia and gout symptoms before the age of 40, which is defined as the pathotype of early-onset gout [15,16]. In addition to environmental factors, genetic predispositions leading to chronic, yet asymptomatic hyperuricemia in childhood and adolescence are considered to be the main causes for the early onset of the disease. Although

**Citation:** Eckenstaler, R.; Benndorf, R.A. The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update. *Int. J. Mol. Sci.* **2021**, *22*, 6678. https://doi.org/10.3390/ ijms22136678

Academic Editor: Thomas Falguières

Received: 31 May 2021 Accepted: 18 June 2021 Published: 22 June 2021

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not every patient with hyperuricemia necessarily develops gout [17], it is considered to be the major risk factor for the development and progression of the disease. In this review, we will specifically address the pathogenesis and genetic background of early-onset gout and highlight the role of intestinal uric acid transport in this context.
