Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants

Simon A Jones, Vassili Valayannopoulos, Eugene Schneider, Stephen Eckert, Maryam Banikazemi, Martin Bialer, Stephen Cederbaum, Alicia Chan, Anil Dhawan, Maja Di Rocco, Jennifer Domm, Gregory M Enns, David Finegold, J Jay Gargus, Ornella Guardamagna, Christian Hendriksz, Iman G Mahmoud, Julian Raiman, Laila A Selim, Chester B Whitley, Osama Zaki, Anthony G Quinn, Simon A Jones, Vassili Valayannopoulos, Eugene Schneider, Stephen Eckert, Maryam Banikazemi, Martin Bialer, Stephen Cederbaum, Alicia Chan, Anil Dhawan, Maja Di Rocco, Jennifer Domm, Gregory M Enns, David Finegold, J Jay Gargus, Ornella Guardamagna, Christian Hendriksz, Iman G Mahmoud, Julian Raiman, Laila A Selim, Chester B Whitley, Osama Zaki, Anthony G Quinn

Abstract

Purpose: The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.

Methods: Investigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan-Meier survival analyses were conducted for the overall population and for treated and untreated patients.

Results: Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).

Conclusions: These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.Genet Med 18 5, 452-458.

Figures

Figure 1
Figure 1
Spaghetti plot of (a) alanine aminotransferase (ALT) and (b) bilirubin changes over time in infants with lysosomal acid lipase deficiency.
Figure 2
Figure 2
Kaplan–Meier plot of time from birth to death in the (a) overall population and (b) infants with early growth failure. Top line is “Upper 95% Confidence Limit”, Middle line is “Survival Function Estimate” and bottom line is “Lower 95% Confidence Limit”.

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