Lysinuric Protein Intolerance as a Mimicker of Juvenile Myelomonocytic Leukemia and Hemophagocytic Lymphohistiocytosis
2Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer
3Pediatric Nephrology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer
4Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
A 10 weeks old girl presented with 1 month of vomiting after every meal. Her family history raised suspicion of genetic disease. Physical examination revealed splenomegaly, hypotonia and petechial rash. Findings on blood tests were consistent with HLH versus JMML. These included bicytopenia, hyperferitinemia, elevated LDH, hypertriglyceridemia and blood smear that showed many immature myeloid forms (both monocytic and erythroid) and several blasts. As part of systemic workup, she underwent abdominal ultrasound demonstrating enlarged kidneys which prompted further investigation in the direction of metabolic disease. Ammonia levels were elevated and amino acid analyses revealed low plasma concentration and increased urinary excretion of lysine, arginine, and ornithine. Due to this findings Lysinuric Protein Intolerance (LPI) was suspected. Whole exome sequencing Confirmed the diagnosis.
LPI is a metabolic disease caused by impaired amino acid transport. Findings are variable and multisystemic and may include recurrent vomiting, failure to thrive, hepatosplenomegaly, hypotonia, involvement of the lungs and the kidneys, hematologic abnormalities and presentation resembling hemophagocytic lymphohistiocytosis (HLH).
Our patient was treated with protein low diet and citrulline and within 2 weeks there was great improvement in her symptoms.
Metabolic diseases such as LPI must be taken into consideration as a differential diagnosis of HLH and JMML, and a careful metabolic workup should be performed to such patients.