Transformation of a long-standing phosphaturic tumor-inducing osteomalacia into malignancy.

Key Clinical Message: Tumor-induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting and deranged bone turnover. Clinicians should consider tumor-induced osteomalacia in unexplained hypophosphatemia and investigate for underlying tumors. Abstract: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, which leads to deranged bone turnover. TIO is usually associated with benign mesenchymal tumors, although it has also been reported in malignant tumors. We present the case of a 56-year-old individual who experienced a protracted 6-year clinical course characterized by hypophosphatemia, weakness, and kyphosis, alongside the presence of a foot tumor. Subsequently, this lesion displayed malignant behavior and was ultimately diagnosed as a high-grade sarcoma. To date, this case is among the 10 reported cases in the literature of a mesenchymal tumor associated with TIO undergoing malignant transformation. This report underscores the importance of a comprehensive evaluation of patients with unexplained hypophosphatemia and highlights the need for diligent follow-up to detect possible malignant transformation of the underlying tumor. Clinicians should consider TIO in the differential diagnosis of hypophosphatemia and promptly investigate for the presence of an underlying tumor, as early detection may improve the patient's prognosis.

A novel mutation c.457C > T p.Q153 in the HMBS gene in a Mexican woman with acute intermittent porphyria.

Key Clinical Message: The detection of a novel HMBS gene mutation (c.457C > T) in a Mexican woman with acute intermittent porphyria underscores the importance of expanding genetic analyses in diverse populations to improve diagnosis, management, and knowledge of the disease's clinical implications. Abstract: Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a deficiency in the enzymatic activity of porphobilinogen deaminase (HMBS), resulting in the accumulation of toxic heme metabolites. In this report, we present the case of a Mexican woman with AIP who experienced recurrent episodes of severe abdominal pain, weakness, vomiting, and insomnia. Despite the challenges in diagnosis and treatment, genetic analysis revealed a novel HMBS mutation, c.457C > T (p.Q153X), located in exon 9. This mutation induces a premature translational stop codon and had not been previously reported in medical literature among individuals with AIP. Remarkably, the patient exhibited a positive response to RNA interference therapy. We hypothesize that this novel HMBS mutation may potentially account for the more severe clinical presentation observed in this case. However, further research is necessary to establish a definitive link between this specific mutation and disease severity. The prevalence and genetic variants of AIP in Mexico remain largely unknown, underscoring the importance of conducting additional research and expanding genetic analyses to gain a better understanding of the clinical implications associated with these mutations.