Dear editor, We read with interest the article entitled ‘Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease’written by Uhlig1 and published by Gut. The study, describing the very early onset of intestinal inflammation in several orphan monogenic diseases, aimed at determining the presence of a link between the IBD-like phenotype shown by these rare diseases and the intestinal inflammation seen in typical IBD. The IBD aetiology is multifactorial: at present, genome-wide association studies have identified 163 susceptibility loci associated with an increased risk of developing IBD. 2 Beside these identified genetic loci that provide little contribution to explain IBD hereditability, the number of monogenic diseases presenting IBD-like symptoms is however continuously increasing. These monogenic diseases usually exhibit very early onset and very severe symptoms; in addition, they are often unresponsive to common drugs (anti-inflammatory and immunosuppressive treatments, such as anti-TNFα).

In his article, 1 Uhlig reports that children with very early onset of bowel inflammation may present a different phenotype and a different genetic architecture. In particular, these children can be classified either as classical IBD patients or as patients suffering from monogenic diseases, the latter also carrying a high number of genetic variants associated with susceptibility to develop IBD. In this regard, we wish to focus the attention on six patients suffering from mevalonate kinase deficiency(MKD, OMIM# 260920), diagnosed during the first year of life and followed-up at the Institute for Maternal and Child Health—IRCCS ‘Burlo Garofolo’(Trieste, Italy). MKD, caused by inherited recessive mutations in the mevalonate kinase gene (MVK), is characterised by febrile attacks, often associated with abdominal pain, diarrhoea and vomiting; it can be considered as an auto-inflammatory defect predisposing to IBD-like intestinal inflammation. 3 4 The six MKD patients were homozygous and/or heterozygous for missense mutations on the MVK gene (table 1).