Early diagnosis of infantile-onset lysosomal acid lipase deficiency in the advent of available enzyme replacement therapy

Jennifer L Cohen,Jessica Burfield,Angela Samuels,Arianna K Stefanatos,Can Ficicioglu,Helio Pedro,Karen Valdez-Gonzalez,Marc Yudkoff

doi:10.1186/s13023-019-1129-y

Abstract

BackgroundLysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form also known as Wolman disease. We sought to determine the outcomes and clinical needs of infants diagnosed with LAL-D, treated with enzyme replacement therapy (ERT).MethodsA chart review was conducted on two infantile-onset LAL-D patients to determine clinical outcomes based on laboratory results, abdominal imaging, growth and dietary records, cardiology, endocrinology, ophthalmology, hematology, and neurocognitive evaluations.ResultsTwo patients, both diagnosed and treated before 6 months old, demonstrated clinical improvement following weekly ERT. They required dosage increases to optimize growth and symptomatology. Both received a formula low in long chain triglycerides and high in medium chain triglycerides, an intervention that allowed significant catch-up growth. Patient 1 required treatment for partial adrenal insufficiency and hypothyroidism. Both patients demonstrated reduction in liver and spleen size and varying degrees of improved liver function. Neither experienced serious adverse reactions to ERT.ConclusionERT has led to longer and healthier survival of affected infants. It is imperative that dietary interventions and systemic clinical care become integral to the management. Continued evidence of survival and clinical improvement in this population, coupled with available mass spectrometry enzyme assay from dried blood spots, raises the question of this rare and possibly underdiagnosed disorder’s candidacy for newborn screening.

Highlights

Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form referred to as Wolman disease (OMIM #278000) [1]
Both patients demonstrated absent lysosomal acid lipase enzyme activity as well as confirmed pathogenic variants in LIPA with targeted gene sequencing. Their parallel presentations of failure to thrive secondary to feeding difficulties and gastrointestinal symptoms, coupled with hepatomegaly and adrenal calcifications, are consistent with the classic presentation of this disease [12]
After 22 months of enzyme replacement therapy (ERT), Patient 1 experienced a 59% reduction in aspartate aminotransferase (AST) and a 32% reduction in ALT; the total bilirubin and alkaline phosphatase were within normal limits prior to ERT

Summary

Introduction

Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form known as Wolman disease. We sought to determine the outcomes and clinical needs of infants diagnosed with LAL-D, treated with enzyme replacement therapy (ERT). Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form referred to as Wolman disease (OMIM #278000) [1]. Prior to the advent of enzyme replacement therapy (ERT) with a recombinant form of lipoprotein lipase, sebelipase alfa (Kanuma®), life expectancy was typically less than twelve months [2]. Cohen et al Orphanet Journal of Rare Diseases (2019) 14:198 rapidly progressive LAL-D, a patient was increased to 5 mg/kg weekly at week 88 of treatment [9]. Other data underscore a need to be attentive to adrenal complications that may occur in utero [10, 11]

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