In a letter to the editor of Pediatric Blood & Cancer, researchers presented the case report of 2 infants with hemophagocytic lymphohistiocytosis associated with Wolman disease, a type of lysosomal acid lipase deficiency (LAL-D).

The 2 children were treated based on information obtained from rapid whole-genome sequencing. 

Hemophagocytic lymphohistiocytosis is characterized by severe systemic hyperinflammation, with the most common symptoms being pyrexia, hepatosplenomegaly, and derangement of biomarkers such as ferritin and triglycerides. Prognosis is poor, with the mortality rate reportedly as high as 30%. 

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One of the cases presented was that of a 2-month-old who presented with intermittent vomiting lasting for 1 month. This progressed to fever, abdominal distension, and tachypnea. Upon admission, the patient was found to have hepatosplenomegaly, and blood results were consistent with a diagnosis of hemophagocytic lymphohistiocytosis. 

Read more about LAL-D etiology 

The patient’s physicians started the patient on dexamethasone and etoposide. The child was also found to have concomitant cytomegalovirus infection, which was treated with ganciclovir. His abdominal distension and ascites worsened, resulting in respiratory decompensation. The child was transferred to the intensive care unit for noninvasive ventilation. 

A chest X-ray revealed bilateral adrenal calcifications, which raised clinical suspicions of Wolman disease. The patient’s physicians advised the mother to stop breastfeeding; parenteral lipids were ceased and a minimal-fat formula was commenced. Pending diagnostic confirmation, the child was granted compassionate access to sebelipase alfa. 

Diagnostic tests revealed a homozygous likely pathogenic missense variant, c.524A>G; p.(Gln175Pro), in the LIPA gene—a result of paternal uniparental isodisomy. This was enough diagnostic confirmation for the commencement of enzyme replacement therapy. Unfortunately, the child’s clinical condition worsened with impaired liver function, viraemia, and bacteraemia and the child died 3 weeks later. 

“Over the next decade, genomic sequencing may become integrated into newborn screening programmes, providing a pathway for pre-symptomatic diagnosis and treatment,” the authors wrote. 


Selvanathan A, Forwood C, Russell J, et al. Rapid whole-genome sequencing leading to specific treatment for two infants with haemophagocytic lymphohistiocytosis due to Wolman diseasePediatr Blood Cancer. Published online April 24, 2023. doi:10.1002/pbc.30394