A case report recently published in Pediatric Blood and Cancer describes a female infant who was diagnosed with severe systemic mastocytosis (SM) caused by the D816V KIT gene mutation.
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
SM is very rare in children, occurring in fewer than 1% of cases. This can result in misdiagnosis, especially when individuals present with symptoms that could be attributed to several diseases.
The patient was originally diagnosed with an enlarged liver and spleen before birth and was born at 35 weeks and one day gestation via Cesarean section. Due to lung underdevelopment, the patient required ventilation from birth to assist with breathing.
Read more about SM causes and risk factors
After birth, the infant’s abdomen appeared very swollen with a raised, purple rash. The rash continued to worsen throughout the first week of life.
An ultrasound was then performed, which confirmed the enlarged liver and spleen and showed signs of cirrhosis. Blood testing revealed significant liver dysfunction and low levels of platelets.
Skin and liver biopsies displayed mast cell infiltration and high levels of the KIT protein. Genetic testing confirmed the diagnosis of SM with a KIT D816V mutation. While KIT mutations are very prevalent in both children and adults with SM, this specific mutation only occurs in about one-third of children with the disease, the authors noted.
The mutation was found in several tissues, including the skin, bone marrow, blood and umbilical cord, indicating its presence in all cells of the body. This is known as a germline mutation, and is not usually observed in SM. Neither parent tested positive for the mutation, indicating that it occurred spontaneously in the patient.
Although few studies have investigated the effects of midostaurin (a KIT-targeting drug) in children, it often works well in adults with SM. Therefore, the authors prescribed midostaurin and the chemotherapy drug cytarabine to the patient. Over time, prednisolone, cetirizine, ranitidine and montelukast were added to the treatment regimen to help stabilize her mast cells.
Following treatment, inflammation and skin crusting decreased, but the organs remained enlarged, and the patient remained reliant on the ventilator.
The authors considered a stem cell transplant, but decided against the procedure due to the patient’s poor health. Ultimately, she died of respiratory and circulatory failure at 86 days of age.
“To the best of our knowledge, this is the first report of an SM patient with a germline KIT mutation p.D816V, with fatal outcome despite effective treatment with the KIT antagonist midostaurin,” the authors wrote.
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