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

Abstract

Background Lysosomal 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). Methods A 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. Results Two 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. Conclusion ERT 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. Electronic supplementary material The online version of this article (10.1186/s13023-019-1129-y) contains supplementary material, which is available to authorized users.

Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up

“…As reported previously [ 28 ], and confirmed in this report, early WD diagnosis enables precocious ERT initiation and better clinical outcome. Optimized methods are available to perform WD screening on dried blood spot [ 29 , 30 ].…”

Early diagnosis and successful long-term management of a rare, severe lysosomal acid lipase deficiency/Wolman disease patient: Infancy to age five

“…Our case demonstrated bilateral echogenic adrenal glands on fetal ultrasound at gestational week 34 and postnatally, similar to another case of an infant with LAL-D (6), suggesting a potential early diagnostic feature. A diet high in MCT fat was associated with optimized growth, consistent with findings in infants with severe LAL-D who received sebelipase alfa treatment (7,8).…”

Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases

“…The Wolman disease symptoms include mental deterioration, enlarged liver and spleen, distended abdomen, gastrointestinal problems, jaundice, anemia, vomiting, calcium deposition in adrenal glands, and hypothyroidism [ 31 , 32 , 202 ]. Clinically, LAL deficiency results in two major phenotypes, i.e., infantile-onset Wolman disease and later-onset cholesteryl ester disease, and correlates with higher residual LAL activity relative to Wolman disease.…”