Joint manifestations revealing inborn metabolic diseases in adults: a narrative review

Abstract

Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as “bone crises”. Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as “enzymopathic gouts”. Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson’s disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.

Towards Personalized Treatment in Haemophilia: The Role of Genetic Factors in Iron and Heme Control to Identify Patients at Risk for Haemophilic Arthropathy

“…Hepcidin, the expression of which is regulated by HFE (high iron (Fe)), inhibits oral iron absorption [20]. Genetic mutations in HFE are common among the Caucasian population [21] and are associated with iron overload and the development of osteoarthritis with some features resembling HA [22][23][24][25]. Cases of arthropathy in haemochromatosis and haemophilia alike are characterized by cartilage degeneration, subchondral bone changes with osteophyte and cyst formation, and osteoporosis.…”