Genetic predisposition of Asparaginase-induced hypertriglyceridemia in children with acute lymphoblastic leukemia: Two case reports and review of literature

Table 1 Cholesterol, triglycerides and high-density lipoproteins levels at different time points after asparaginase treatment of patient 1

Patient 1	Reference interval	Before PEG-ASP therapy	PEG-ASP therapy
			Day 7	Day 14	Day 21	Day 28
CHOL (mmol/L)	3.10-5.20	3.16	15.90	17.80	2.29	5.50
TG (mmol/L)	0.00-1.69	1.06	NA	60.00	42.10	6.08
HDL (mmol/L)	1.17-1.55	1.67	0.31	1.44	1.31	1.89

PEG-ASP: Pegylated asparaginase; CHOL: Cholesterol; TG: Triglycerides; HDL: High-density lipoproteins; NA: Not available.

Table 2 Cholesterol, triglycerides and high-density lipoproteins levels at different time points after asparaginase treatment of patient 2

Patient 2	Reference interval	Before PEG-ASP therapy	PEG-ASP therapy
			Day 12	Day 14	Day 21	Day 31
CHOL (mmol/L)	3.10-5.20	NA	13.39	3.97	4.87	4.99
TG (mmol/L)	0.00-1.69	NA	30.91	2.50	4.38	2.25
HDL (mmol/L)	1.17-1.55	NA	1.17	0.49	0.79	1.32

PEG-ASP: Pegylated asparaginase; CHOL: Cholesterol; TG: Triglycerides; HDL: High-density lipoproteins; NA: Not available.

Table 3 Genetic variants identified in patients with severe hypertriglyceridemia

Patients	Genes	Gene functions	Ref.	Variants	ACMG classification	CADD	GnomAD
Patient 1	LPL	Encodes the main enzyme of triglyceride hydrolysis, lipoprotein lipase	[28,31]	Chr8:g.19948197G>A; NM_000237.3:c.106G>A; NP_000228.1:p.Asp36Asn, rs1801177	Likely benign	19.6	1.6%
Patient 2	LPL	Encodes the main enzyme of triglyceride hydrolysis, lipoprotein lipase	[28,31]	Chr8:g.19956018A>G; NM_000237.3:c.953A>G; NP_000228.1:p.Asn318Ser, rs268	Conflicting classifications of pathogenicity	21.3	1.97%
	APOA5	Encodes apolipoprotein A-V, which activates lipoprotein lipase and participates in the absorption of residual particles and the secretion of very-low-density lipoprotein by hepatocytes	[31]	Chr11:g.116790666T>C; NM_001371904.1:c.563A>G; NP_001358833.1:p.Lys188Arg rs1303929283	Variant of uncertain significance	21.5	0.0009%

ACMG: American College of Medical Genetics and Genomics; CADD: Combined Annotation Dependent Depletion; GnomAD: Genome Aggregation Database.