Burden of Lysosomal Acid Lipase Deficiency

Abstract

Lysosomal acid lipase deficiency (LAL-D) is a rare, underdiagnosed, progressive, systemic disease, generally manifesting early in life. It is a medical emergency in infants and causes significant morbidity and early mortality in children and adults. The objective was to characterize signs and symptoms of LAL-D over time, highlighting evidence gaps to guide future research. A systematic review of published literature describing burden of LAL-D was conducted. Given the paucity of published LAL-D studies, a broad search strategy of English-language studies in Medline/PubMed and EMBASE was performed, without limits by publication date or study design. All studies describing disease burden were included. 701 abstracts were identified; with 194 articles eligible for inclusion. Clinical burden was primarily described in case reports and case series, with 214 cases in 138 articles. Of these, 103 cases were infants (onset of characteristic clinical manifestations before six months of age); the remainder were children/adults. Two-thirds of data provided some longitudinal follow-up, allowing some exploratory analysis of temporal progression. Mean time between symptom onset and diagnosis was two years, with reported prior misdiagnoses of other lipid storage and related diseases in 9% of individuals. The majority of diagnoses were made based on LAL enzyme analysis, either alone (23.8%), in combination with liver biopsy and/or genotyping (49.9%). In all individuals, hepatomegaly was most commonly-reported (82% in infants, 84% in children/adults); hepatomegaly was also the most common factor leading to LAL-D diagnosis. Sixty-two percent of infants had severe morbidity or mortality reported, typically by one year of age. Dyslipidemia and elevated transaminases were frequently reported in all age groups. Very limited data are published on burden of disease in LAL-D. The available reports show substantial disease burden in both infants and in children/adults. Prospective cohort studies or registries are needed to better characterize disease progression.