Stem cell transplant effectively treated pediatric patient with severe metabolic disorder
Allogeneic hematopoietic stem cell transplant appears to be safe and effective for pediatric patients with mevalonate kinase deficiency who respond inadequately to anticytokine drugs, according to a recent case report.
“The prognosis of patients with mevalonic aciduria is usually severe: more than 50% of infants or young children die during a severe multisystemic inflammatory attack,” study researcher Stefano Giardino, MD, the department of pediatric hematology and oncology at Istituto G. Gaslini in Genoa, Italy, and colleagues wrote. “Mevalonate kinase deficiency has also been identified as the cause of an autoinflammatory periodic syndrome called hyperimmunoglobulinemia D, or Dutch-type periodic fever syndrome.”
The researchers characterized a case of a severe phenotype of mevalonate kinase deficiency affecting a male aged 2 years and 10 months, who was born a monochorionic twin at 37 weeks’ gestation to consanguineous parents. The twin brother had died at 18 months from severe bleeding after a liver biopsy, which revealed an “unspecific chronic inflammatory infiltrate.”
The surviving sibling underwent first-line therapy with ibuprofen, prednisone and supportive care, but the therapy did not inhibit further febrile attacks. The addition of anakinra, a subcutaneous recombinant IL-1 receptor antagonist, at 1.5 mg/kg/daily, prompted a partial response, but was discontinued after the patient developed severe pneumonia and sepsis caused by Streptococcus pneumoniae.
The patient then underwent hematopoietic stem cell transplantation (HSCT), which was considered the only curative option. The patient achieved complete immunologic recovery (CD4 >500/mmc) with no additional need for immunoglobulin replacement therapy at 6 months after transplantation. At 12 months after HSCT, immunosuppressive therapies were discontinued, with no signs of chronic graft-versus-host disease and with stable full donor chimerism. No febrile episodes caused by inflammatory activation occurred after HSCT.
At 5 years after HSCT, the patient continued to demonstrate a positive clinical profile and good quality of life, with normal neurologic and psychomotor skills. An MRI of the brain performed 1 year after HSCT was normal. The patient, now aged 7 years, speaks fluently and attends age-appropriate school, and has demonstrated adequate growth, reaching the third percentile for height and weight.
“In our opinion, this case is relevant because it confirms that anticytokine drugs alone are not sufficient for the management of patients with severe [mevalonate kinase deficiency] phenotype and that allogeneic HSCT remains the only effective cure,” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.