Lysosomal acid lipase deficiency in children: dynamics of clinical and laboratory parameters on the background of enzyme replacement therapy

Background. Lysosomal acid lipase deficiency (LALD) is a chronic, progressive disease based on a defect in the LIPA gene encoding lysosomal acid lipase, leading to impaired lipid metabolism. Currently, enzyme replacement therapy (ERT) has been developed.

Objective. To evaluate the dynamics of clinical and laboratory symptoms of LALD in children on the background of ERT with sebelipase alpha.

Materials and methods. A retrospective analysis of the medical records of 5 children with LALD (boys – 2, girls – 3) who received sebelipase alpha therapy according to the instructions was carried out. The dynamics of anthropometric parameters were assessed (height, weight, body mass index (BMI), SDS BMI, biochemical blood test with assessment of transaminase levels (ALT, AST), lipidogram, ultrasound examination of abdominal organs, liver elastometry.

Results. 3 (60%) children had signs of malnutrition and a decrease in SDS BMI of less than -1 before starting therapy. In 2 (40%) children, after 1 year of ERT, this indicator returned to normal, in 1 child after 2 years. Before the start of ERT, all children had an increase in ALT levels: in 3 (60%) children – up to 2 norms, and in 1 child – from 2 to 3 norms and more than 4 norms, AST: in 4 (80%) children – less than 2 norms, in 1 child – more than 3 norms. After 1 year from the start of ERT, all children (100%) showed a decrease in the level of transaminases, after 3 years normalization of these indicators was registered in 4 (80%) children, in 1 child transaminases remained elevated during 4 years of follow-up, although they had lower values than before the start of ERT. After 1 year from the start of therapy, all children showed a reduction in liver size. In 1 child, organ size returned to normal after 4 years of therapy, and in 4 (80%) children, hepatomegaly persisted throughout the follow-up, although it became significantly less than before the start of ERT. The METAVIR fibrosis score before the start of FGT in 2 (40%) children was F1, in 1 child – F2, and in 1 child – F3. After 2 years, it decreased to F0 in all children. The steatosis index in 3 (60%) children is S3, and in 2 children it is S2. Signs of steatosis in 1 child persisted for 8 years of therapy at S3 level, in 1 child for 4 years at S2 level, in 2 (40%) children after 2 years the index of steatosis decreased from S2 to S1, in 1 child – from S3 to S0. There were no signs of liver damage progression on the background of ERT in any child. The size of the spleen was normal in 3 (60%) children 3 years after the start of therapy. No increase in lipid levels above baseline values was detected in any child on the background of ERT: total cholesterol and LDL exceeded the standard values more often, while the level of TG normalized after 3 years of PHT in all children. HDL in 1 child remained below normal even after 4 years of therapy.

Conclusion. A comparative analysis of the clinical, laboratory and instrumental parameters of 5 children with LALD who received sebelipase alpha for 3 years (2 children), 4 years (2 children) and 8 years (1 child) allows us to conclude that there are positive dynamics against the background of therapy in all patients. This is manifested by normalization of body weight-growth indicators, reduction in the size of the liver and spleen, decrease in cytolysis markers, improvement or stabilization of structural changes in the liver parenchyma. There is no progression of dyslipidemia, although the levels of cholesterol and LDL remain elevated in most measurements, but below the initial values, which is explained by a complex mechanism of regulation of lipid metabolism.

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