A 2-month-old infant was diagnosed with Wolman disease (WD), a type of lysosomal acid lipase deficiency (LAL-D), using ultra-rapid genomic sequencing. The case was presented at the 14th International Congress of Inborn Errors of Metabolism in Sydney, Australia.

The infant failed to thrive and presented with a fever, lethargy, and abdominal distension with marked hepatosplenomegaly. Progressive sepsis and liver failure led to haemophagocytic lymphohistiocytosis (HLH), a condition described in several cases of WD.

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The presence of HLH together with the observation of marked adrenal calcification on chest radiography raised the suspicion of WD. Ultra-rapid genomic testing identified a homozygous, likely pathogenic missense variant (c.524A>C) in the LIPA gene.

The analysis was performed with the aim of the Acute Care Genomics study, a national initiative supported by the Australian Genomics Health Alliance, and the results were obtained within 4 days. Additional studies suggested paternal isodisomy of chromosome 10.

The infant initiated enzyme replacement therapy (ERT) with sebelipase alfa (2 doses per week). In addition, breastfeeding was ceased and substituted by low-fat formula due to issues with fat metabolism. The infant continued on high-dose dexamethasone and ceased etoposide.

Sebelipase Alfa Could Be Life-Saving for Children With Wolman Disease

Unfortunately, the disease progressed, which lead to fulminant liver failure, hyperammonaemia and sepsis, coagulopathy, portal hypertension, and refractory gastrointestinal bleeding.

“Two and a half weeks after diagnosis the infant died, aged 3 months due to underlying critical illness,” the authors said.

Reference

Forwood C, Macintosh R, Russell J, et al. Ultra-rapid genomic diagnosis offers treatment options for Wolman disease and also reveals complex underlying genetic mechanism. Poster presented at: 14th International Congress of Inborn Errors of Metabolism: November 21-23, 2021; Sydney, Australia.