Weekly oral alendronate in mevalonate kinase deficiency

Abstract

BackgroundMevalonate kinase deficiency (MKD) is caused by mutations in the MVK gene, encoding the second enzyme of mevalonate pathway, which results in subsequent shortage of downstream compounds, and starts in childhood with febrile attacks, skin, joint, and gastrointestinal symptoms, sometimes induced by vaccinations.MethodsFor a history of early-onset corticosteroid-induced reduction of bone mineral density in a 14-year-old boy with MKD, who also had presented three bone fractures, we administered weekly oral alendronate, a drug widely used in the management of osteoporosis and other high bone turnover diseases, which blocks mevalonate and halts the prenylation process.ResultsAll of the patient’s MKD clinical and laboratory abnormalities were resolved after starting alendronate treatment.ConclusionsThis observation appears enigmatic, since alendronate should reinforce the metabolic block characterizing MKD, but is crucial because of the ultimate improvement shown by this patient. The anti-inflammatory properties of bisphosphonates are a new question for debate among physicians across various specialties, and requires further biochemical and clinical investigation.

Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

“…To assess the effects of thiopurine treatment, some CD patients were recruited immediately prior to commencing AZA therapy, and longitudinal blood sampling was conducted over a followup period of 6 months. The analyses of Vδ2 T cell subset distribution in peripheral blood were conducted in a subgroup of pediatric CD patients (mean age, 13 years [range [7][8][9][10][11][12][13][14][15][16][17][18][19]; 50% male; CRP, mean 12.5 mg/l [range 5-39 mg/l]) and sex/age/ethnicity-matched IBS controls (mean age, 13 years [range [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]; 50% male; CRP, <5 mg/l) in order to limit the effects of demography, historical pathogen exposure, and concomitant therapies.…”

“…PAg are produced by a wide range of bacteria that can colonize the gut (1) and can also accumulate in host cells due to dysregulation of the mevalonate kinase metabolic pathway during malignant transformation or microbial infection (5,6). Intriguingly, human patients with mutations in the mevalonate kinase gene exhibit a severe neonatal colitis that can be successfully treated with bisphosphonate drugs, which modulate PAg synthesis and alter Vδ2 T cell function in vivo (7)(8)(9)(10). We recently reported that PAg exposure stimulates human blood Vδ2 T cells to upregulate the gut-homing integrin α4β7, and we identified Vδ2 T cells in human colonic biopsies that produced proinflammatory cytokines and enhanced IFNγ synthesis by intestinal CD4 + T cells (11).…”

Key facts and hot spots on tumor necrosis factor receptor‐associated periodic syndrome

“…However, a partial loss of efficacy in a TRAPS patient who received canakinumab has recently been described: surprisingly, when alendronate was added to canakinumab, in order to treat a concomitant corticosteroidinduced osteoporosis, disease activity was promptly and fully controlled [110]. These same findings were also strikingly described in a boy with mevalonate kinase deficiency syndrome, a metabolic disorder included in the family of AIDs [111].…”

Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience

“…There is an anecdotal report of disease resolution with oral alendronate, which was initially prescribed to treat osteoporosis in a 14-year-old boy with HIDS [8]. Bisphosphonates inhibit the already compromised MVK pathway [38] and are, therefore, considered as contraindicated in HIDS.…”