Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies

Suresh Vijay; Anais Brassier; Arunabha Ghosh; Simona Fecarotta; Florian Abel; Sachin Marulkar; Simon A. Jones

doi:10.1186/s13023-020-01577-4

Orphanet Journal of Rare Diseases

Table 5 LIPA genotype (assessed by central laboratory)

From: Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies

Study	Patient #	Allelic mutations	Effects of mutation	Variant severity
VITAL
	1	ND	NA	NA
	2	c.46A > C HOM C c.676-42G > A HET c.966 + 46C > T HET c.894G > A HET c.455 T > C HET	p.Thr16Pro rs1051338 Intronic rs1556478 Intronic rs3802656 p.Gln298Gln rs116928232 p.Leul52Pro	Common variant Common variant Common variant Documented pathogenic VUS
	3	c.884A > G HET	p.His295Arg	VUS
	4	c.539-5C > T HET c.482delA HET c.538G > A HET	Intronic rs2297472 p.Asn161Ilefs*19 p.Gly180Ser	Common variant Documented pathogenic VUS
	5	c.539-5C > T HET c.676-42G > A HOM c.966 + 46C > T HOM c.193C > T HET c.894G > A HET c.419G > C HOM	Intronic rs2297472 Intronic rs1556478 Intronic rs3802656 p.Arg65Stop p.Gln298Gln rs116928232 p.Trp140Ser	Common variant Common variant Common variant Documented pathogenic Documented pathogenic VUS
	6	c.676-2A > G HOM	Intronic	Documented pathogenic
	7	c.350_351insCC HET c.797G > T HET	p.Met117IlefsStop45 p.Gly266Val	Expected Pathogenic VUS
	8	ND	NA	NA
	9	c.67G > A HOM c.539-5C > T HET c.260G > T HOM	p.Gly23Arg rs1051339 Intronic rs2297472 p.Gly87Val	Common variant Common variant Documented pathogenic
CL08
	1	c.594dupT HOM	p.Ala199Cysfs*13	Documented pathogenic
	2^a,b	c.67G > A HOM c.539-5C > T HOM	p.Gly23Arg Intronic	Common variant Common variant
	3	ND	NA	NA
	4	ND	NA	NA
	5^a	ND	NA	NA
	6^a	ND	NA	NA
	7	c.229G > T HOM	Intronic	Documented pathogenic
	8	ND	NA	NA
	9	c.46A > C HOM c.658C > T HOM c.539-5C > T HOM c.894 + 1G > A HOM	p.Thr16Pro p.Pro220Ser Intronic Splicing	Common variant VUS^c Common variant Documented pathogenic
	10	c.892C > T^d	p.Gln298*	Documented pathogenic

HET heterozygous, HOM homozygous, NA not applicable, ND not done, VUS variant of unknown significance
^aPatient was homozygous for whole LIPA deletion, including the neighboring gene for cholesterol 25-hydroxylase, CH25H, based on testing at a local laboratory
^bGene sequencing data from the central laboratory identified 2 polymorphisms, both common variants for the patient. It is recognized that the results from the central and local laboratories are discrepant, in that allelic variants should not have been detected in a patient who is homozygous for a whole LIPA deletion. Investigation into the cause of this discrepancy is ongoing
^cNovel missense mutation
^dThe testing laboratory did not report whether the patient was heterozygous or homozygous for the given allelic mutation; however, both parents were heterozygous for this mutation

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ISSN: 1750-1172

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