Case Report: Mevalonic Aciduria Complicated by Acute Myeloid Leukemia After Hematopoietic Stem Cell Transplantation

Abstract

Mevalonic aciduria (MA) is the most severe clinical subtype of mevalonate kinase deficiency (MKD) caused by an inherited defect in the mevalonate pathway. The treatment of MKD focuses on the suppression of recurrent hyperinflammatory attacks using anti-inflammatory drugs. Recently, allogeneic hematopoietic stem cell transplantation (HCT) was shown to successfully ameliorate autoinflammatory attacks in patients with MKD. Here, we report a case of an infant who showed severe recurrent systemic inflammation and was diagnosed with MA. Although she responded to steroids, her symptoms relapsed after the dose was tapered, and organ deterioration occurred. Therefore, at the age of 11 months, HCT from a matched, unrelated donor was performed for curative treatment. However, at 50 days after transplantation, acute myeloid leukemia was diagnosed, which was chemo-refractory. A second HCT from her haploidentical father was performed to treat the acute myeloid leukemia, but the patient died of sepsis on day 4 after transplantation. This is the first report of malignancy following HCT for MA. Our findings suggest that normalizing the mevalonate pathway after HCT in patients with MKD impacts patients differently depending on the clinical spectrum and severity of disease.

Tocilizumab effectively reduces flares of hyperimmunoglobulin D syndrome in children: Three cases in China

“…According to previous reports, hematopoietic stem cell transplantation is also an effective method for treating severe HIDS [ 6 , 7 ]. However, severe symptoms related to transplantation may be life-threatening [ 37 ]. Moreover, there may be recurrence after transplantation [ 38 ].…”

Porokeratoses—A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants

“…Alterations in the aforementioned genes, causing the downregulation of the corresponding protein expression, have been reported to produce mevalonate deficiency, resulting in abnormal apoptosis in the keratinocytes. MVK deficiency is an autosomal recessively inherited disease that has three different clinical presentations: DSAP, hyper IgD syndrome and mevalonic aciduria [78,96,[100][101][102][103][104]. It was reported that the DSAP severity closely correlates with the MVK level [96,105].…”

“…Analysis of genomic variants of the mevalonate pathway in porokeratosis showed that the most frequent mutations found in DSAP were in the MVK (26/130 patients) and MVD (56/130 patients) [15]. At least MVK deficiency is an autosomal recessively inherited disease that has three different clinical presentations: DSAP, hyper IgD syndrome and mevalonic aciduria [78,96,[100][101][102][103][104]. It was reported that the DSAP severity closely correlates with the MVK level [96,105].…”