Substrate reduction therapy with miglustat for type 1 Gaucher disease: A retrospective analysis from a single institution

Figures & data

Table I. Patient characteristics.

Pt	Sex/Age (y)^a	GBA1 gene mutations	Age at Dx (y)	SPC/Age (y)	Duration of ERT (y)	SMG	BD
1	F/21	c.798C>G/c.1040T >G (novel mutations)	3	Y/5	4	NA	Y, s
2	M/42	c.437C>T/c.1226A >G (S107L/N370S)	3	Y/12	13	NA	Y, s
3	F/56	c.1226A>G/c.1226A >G (N370S/N370S)	55	N	NA	Y	Y, rs
4	M/62	c.721G>A/c.1226A >G (G202R/N370S)	61	N	1	Y	Y, s
5	M/65	c.1226A>G/RecNci (N370S/RecNci)	51	N	NA	Y	Y, rs
6	M/81	c.1226A>G/c.1448T >C (N370S/L444P)	30	Y/32	NA	NA	Y, rs

^aAge at start of miglustat therapy.

Pt = patient; Dx = diagnosis of Gaucher disease; SPC = splenectomy; ERT = enzyme replacement therapy; SMG = splenomegaly; BD = bone disease (rs: radiological signs only; s: symptomatic disease); F = female; M = male; Y = yes; N = no; NA = not applicable.

Table II. Changes in values of selected variables observed during miglustat therapy.

			Values of analyzed variables during miglustat therapy
Pt	Sex/Age (y)^a	Variables	0	2 m	4 m	8 m	12 m	15 m
1	F/21	B-Hb B-PLT S-Ferrititn P-Chito P-CCL18 Ig profile	122 260 202 1189 428 Normal	ND	108 170 636 2392 ND Normal
2	M/42	B-Hb B-PLT S-Ferritin P-Chito P-CCL18 Ig profile	140 116 1255 ND ND ND	ND	ND	127 95 1627 ND ND ^P IgG 19.3	117 107 ND ND ND ND	127 119 2269 ND ND ^P IgG 18.6
3	F/56	B-Hb B-PLT S-Ferritin P-Chito P-CCL18 Ig profile	122 68 833 1549 908 ^P IgM 3.2	119 66 866 446 939 ^P IgM 3.1	NA	125 102 932 292 323 ^P IgM 3.6	NA	133 104 858 323 497 ^P IgM 3.4
4	M/62	B-Hb B-PLT S-Ferritin P-Chito P-CCL18 Ig profile	133 145 ND 3039 628 ^M IgM–λ 1.5	ND	136 145 ND ND ND ^M IgM–λ 2.0
5	M/65	B-Hb B-PLT S-Ferritin P-Chito P-CCL18 Ig profile	124 104 1239 ND‡ ND‡ ^P IgG 14.9	115 180 2389 ND ND ND	109 198 4028 986 1062 ^P IgG 15.2
6	M/81	B-Hb B-PLT S-Ferritin P-Chito P-CCL18 Ig profile	93 20 4408 2168 ND ^M IgG–λ 33	84 19 4047 ND ND ^M IgG–λ 25	90 12 3260 ND ND ^M IgG–λ 24	91 6 ND ND ND ND

^aAge at start of miglustat therapy.

^bThe samples were improperly transported to the laboratory.

Pt = patient; m = months on miglustat therapy; B-Hb = whole blood hemoglobin concentration (control range: 117–153 g/L); B-PLT = whole blood platelet count (control range: 165–387 × 10⁹/L); S-Ferritin = serum ferritin concentration (control range: 10–150 μg/L); P-Chito = activity of plasma chitotriosidase (control range: <40 nkat/L); P-CCL18 = concentration of plasma chemokine (C-C motif) ligand 18/pulmonary and activation-regulated (control range: <100 μg/L); ND = not determined; NA = not applicable (analyses done at the other laboratory); Ig = immunoglobulin (g/L); ^P = polyclonal; ^M = monoclonal.

Table III. Adverse events and body weight changes observed on miglustat therapy.

Pt	Sex/Age (y)^a	Duration of SRT (months)	Adverse events	Absolute weight loss on SRT	Maximal percentage body weight change as compared to baseline
1	F/21	4	Diarrhea, poor appetite, weight loss	6 kg	–11%
2	M/42	15	Diarrhea, weight loss, tremor (moderate), peripheral neuropathy	4 kg	–5%
3	F/56	20^b	Weight loss, tremor (mild)	5 kg	–8%
4	M/62	3	Weight loss, tremor (mild)	3 kg	–4%
5	M/65	4	Diarrhea, poor appetite, weight loss, tremor (mild)	10 kg	–16%
6	M/81	8^c	Diarrhea, poor appetite, weight loss^d, tremor (mild), peripheral neuropathy^d	12 kg	–18%

^aAge at start of miglustat therapy.

^bStill on miglustat therapy.

^cThe pt died on ERT + SRT therapy due to acute myeloid leukemia.

^dPossible multifactorial etiology (see comment in text).

Pt = patient; SRT = substrate reduction therapy with miglustat; F = female; M = male.