Table 1 Summary of RMCH multimodal group (patient 1–5)

Age at start of ERT (months)

4

2

1

4

3

Age at HCT (months)

8

25

31

7

48

LAL activity at diagnosis (nmol/mg/h)

51

65

51

93

44

Pathogenic variant

Missense variant. homozygous

Deletion: chr10:90,947,449–91,060,391 (112 kb) (hg19). Complete LIPA gene deletion. homozygous

Deletion: chr10:90,947,449–91,060,391 (112 kb) (hg19). Complete LIPA gene deletion. homozygous

c.684delT [p.(Phe22Leufs*13)] LIPA exon 4 deletion (frameshift)—compound heterozygous

Deletion: chr10:90,947,449–91,060,391 (112 kb) (hg19). Complete LIPA gene deletion. homozygous

Indications for HCT

Suboptimal response to treatment and ongoing HLH

Suboptimal response to treatment with ADA and poor central venous access

Suboptimal response to treatment with ADA

Intolerance to ERT—anaphylaxis

Suboptimal response to treatment with ADA

Conditioning

Treosulfan, cyclophosphamide, ATG

Treosulfan, Thiotepa, Fludarabine, Alemtuzumab

Treosulfan, Thiotepa, Fludarabine, Alemtuzumab

Treosulfan, Thiotepa, Fludarabine, Alemtuzumab

Treosulfan, Thiotepa, Fludarabine, ATG

Donor cell source

PBSC matched family

Bone marrow matched sibling

PBSC haploid αβ and CD19 deplete

Bone marrow matched unrelated

Umbilical cord matched unrelated

HCT acute complications

Mild VOD

Nil

Nil

Mild VOD, acute skin GvHD (grade 2)

Engraftment syndrome, acute skin GvHD (grade 2)

Survival (age as of August 2020)

Died aged 13 months

Alive—6 years 5 months old

Alive—5 years 3 months old

Alive—2 years 8 months old

Alive—4 years 10 months old

Peripheral blood chimerism 4w post HCT

100%

100%

100%

100%

100%

Peripheral blood chimerism current

NA

26.3% static

30.2% static

14.5% static

100%

Current LAL activity (nmol/mg/h)

NA

200

165

101

469

Current ERT dose post HCT

NA

1 mg/kg alternate weeks

3 mg/kg alternate weeks

5 mg/kg weekly

3 mg/kg weekly