Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database

Imrie, Jackie; Heptinstall, Lesley; Knight, Stephen; Strong, Kate

doi:10.1186/s12883-015-0511-1

Table 5 Patients with juvenile neurological onset

From: Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database

Patient number/Gender	Sibship	Date of birth	Age at diagnosis	Age at last FU (y, m)/death^c	Neonatal LD	HS/S	Seizures/cataplexy	VSGP	Dev. delay/cognitive problems	Ataxia	Swallowing problems	Psychiatric disturbance	Slurred speech	Miglustat?	Age at 1^st miglustat start	Miglustat duration	Genetic mutations
66/F	–	1970	24y 5 m	41y 2 m	No	Yes	C 24y	12y	11y	24y	24y	32y	24y	Yes	32y	–	c.1211G > A(p.Arg404Gln)/?^d
67/F	–	1995	10y 1 m	16y 3 m	No	No	E 10y 3 m	10y 1 m	8y	10y	13y	No	Yes	Yes	12y	4y	c.1552C > T(p.Arg518Trp)/c.283 T > C(p.Ser95Pro)
68/F	–	1996	10y 6 m	15y 1 m	–	–	<10y	Yes	<10y	<10y	<10y	No	<10y	No	–	–	c.2848G > A(p.Val950Met)/?
69/F	–	1994	14y	17y 10 m	No	No	No	Yes	10y	Yes	Yes	–	6y	No	–	–	c.2974G > T(p.Gly992Trp)/?
70/F	–	1983	14y	21y 11 m^c	No	No	E 12y	Yes	8y	11y	17y	No	Yes	No	–	–	c.3019C > G(p.Pro1007Ala)/?
71^a/M	–	1991	17y	20y 4 m	–	–	E 12y	Yes	At birth	Yes	Yes	Yes	Yes	Yes	18y	2y	c.3019C > G(p.Pro1007Ala)/c.1553G > A(p.Arg518Gln
72/F	–	1986	2 m	25y 10 m	FA LD	At birth	E 14y	11y	11y	14y	15y	No	<14y	No	–	–	c.3176G > A(p.Arg1059Gln)/?
73/M	–	1996	14y	15y 5 m	No	No	No	12y	7y	7y	13y	No	12y	Yes	14y	1y	c.3182 T > C(p.Ile1061Thr)/?
74/M	–	–	7y 5 m	20y^c	PJ	HS	No	7y	6y 5 m	7y	8y	No	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/?
75/F	–	1986	10y	19y 2 m^c	No	No	C 11y	10y	7y	7y	11y	No	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/?
76/M	–	2000	7y	11y 1 m^c	–	–	E 7y	Yes	Yes	Yes	Yes	No	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/?
77^a/F	–	1996	4y 5 m	15y 4 m	PJ	HS 4y 5 m	E 12y	7y	7y	6y	No	No	No	Yes	7y	8y	c.3182 T > C(p.Ile1061Thr)/c.2801G > A(p.Arg934Gln)
78^a/F	–	2002	2 m	9y 10 m	PJ	HS	C 6y	Yes	6y	No	No	No	No	Yes	7y	2y	c.3182 T > C(p.Ile1061Thr)/c.2819C > T(p.Ser940Leu)
79/F	–	1985	4y 1 m	26y 4 m	PJ LD	HS 11y	C 7y E 17y	11y	13y	13y	16y	No	No	Yes	–	–	c.3182 T > C(p.Ile1061Thr)/c.2974G > T(p.Gly992Trp)
80/M	m	1978	12y	18y 8 m^c	No	S 2–10y	E 11y	10y	8y	10y	18y	No	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/c.3019C > G(p.Pro1007Ala
81/M	–	2003	6 m	8y 8 m	PJ LD	HS	–	–	No	–	–	–	–	Yes	7y	1y	c.3182 T > C(p.Ile1061Thr)/ c.3182 T > C(p.Ile1061Thr)
82/M	–	1970	At birth	32y^c	No	No	E 22y	Yes	12y	Yes	27y	No	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/ c.3182 T > C(p.Ile1061Thr)
83/F	–	1991	13y	18y 2 m^c	No	No	No	Yes	10y	14y	14y 5 m	No	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/ c.3182 T > C(p.Ile1061Thr)
84^b/M	–	1988	12y	23y 7 m	No	S 7 y	No	11y 9 m	17y	17y	No	No	No	Yes	21y	2y	c.3182 T > C(p.Ile1061Thr)/ c.3182 T > C(p.Ile1061Thr)
85^b/F	–	1991	6y 5 m	20y 1 m	No	S 5y 5 m	No	8y 3 m	11y 1 m	9y	19y	No	No	Yes	12y	8y	c.3182 T > C(p.Ile1061Thr)/c.3493G > A(p.Val1165Met)
86/F	–	2005	8w	6y 6 m	PJ LD	HS	No	Mild 6y	No	No	No	No	No	Yes	4y	2y	c.3182 T > C(p.Ile1061Thr)/c.350-351delAG
87/F	–	1986	17y	25y 5 m	No	No	E 16y	Yes	5y (FAS)	<16y	<16y	–	Yes	No	–	–	c.3182 T > C(p.Ile1061Thr)/c.3566A > G(p.Glu1189Gly)
88/M	–	1985	18y	26y 7 m	No	S 18 y	No	15y	13y	13y	18y	18y 6 m	18y	Yes	–	–	c.3182 T > C(p.Ile1061Thr)/c.3566A > G(p.Glu1189Gly)
89^a/F	–	1994	10y 4 m	17y 9 m	No	No	C <4y E <17y	<17y	<10y 4 m	<10y 4 m	<17y	No	<17y	Yes	14y	3y	c.3182 T > C(p.Ile1061Thr)/c.410C > T(p.Thr137Met)
90/F	–	1983	15y	22y 8 m^c	PJ	Birth	E 14y	11y	8y	11y	16y	No	Yes	No	–	–	c.3263A > G(p.Tyr1088Cys)/c.1201C > A(p.Pro401Thr)
91/M	–	1989	17y	23y	No	No	No	Yes	8y	9y	18y	17y	17y	Yes	18y	3 m	c.3493A > G(p.Val1165Met)/c.3493A > G(p.Val1165Met)
92/F	b	1990	3 m	17y 2 m^c	PJ	No	E 15y	11y	10y	10y 5 m	15y	No	Yes	Yes	–	–	c.3501C > G(p.Phe1167Leu)/c.3501C > G(p.Phe1167Leu)
93/F	j	1998	10y	13y 6 m	No	No	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	10y	3y	c.3591 + 4delAla/?
94/F	–	1997	10y	14y 8 m^c	No	No	C + E 10y	No	<10y	<10y	Yes Gx	No	Yes	No	–	–	c.3019C > G(p.Pro1007Ala)/c.2464-2465insT
95/M	–	1998	12y	13y 6 m	No	No	C 11y	11y	9y	Tremor 11y	No	No	<5y	Yes	13y	6 m	–
96/F	–	1996	9y	15y 8 m^c	Mild jaundice	S	–	Yes	Yes	Yes	Yes Gx	No	9y	No	–	–	–
97/F	–	1991	16y	17y 6 m^c	–	–	S, C	Yes	<15y	<15y	<17y	No	Yes	No	–	–	–
98/M	–	1967	PM	25y^c	PJ	S 2 y	No	Yes	11y	2y	14y	25y	Yes	No	–	–	–
99/F	–	1972	16y	39y 11 m	PJ	No	No	16y	11y	28y	30y	30y	Yes	Yes	–	–	c.1211G > A(p.Arg404Gln)/c.1133 T > C(P.Val378Ala)
100/M	–	1971	14y	29y 2 m^c	No	13y 5 m	13y	13y 5 m	13y	13y 5 m	13y	No	Yes	No	–	–	–
101/F	–	1963	18y	40y 3 m^c	PJ	No	E 31y	16y	12y	16y	23y	16y	Yes	No	–	–	c.1843C > T(p.Arg615Cys)/c.2972-2973del(p.Gln991ArgfsX15)
102/F	n	–	Teens	23y^c	No	No	–	No	Teens	Teens	Teens	23y	–	No	–	–	c.3182 T > C(p.Ile1061Thr)/?
103/M	–	1987	20y	24y 5 m	No	No	No	<19y	No	13y	22y	No	13y	Yes	22y	2y	c.2861C > T(p.Ser954Leu)/c.3107C > T(p.Thr1036Met)
104/M	–	1972	6y	39y 8 m	No	HS 5y	No	No	No	6y	No	No	No	No	–	–	c.1844G > T(p.Arg615Leu)/c.1844G > T(p.Arg615Leu)
105/M	–	1969	Early 20s	37y 8 m^c	PJ	S 4y	E 30y	Yes	11y	20s	Yes	No	Yes	No	–	–	–
106^a/F	o	1976	27y	35y 10 m	No	No	No	27y	13y	26y	26y	No	27y	Yes	–	–	c.1552C > T(p.Arg518Trp)/c.1552C > T(p.Arg518Trp)
107/M	o	1972	30y	37y 2 m^c	No	No	Teens	26y	26y	26y	27y	25y	26y	No	–	–	c.1552C > T(p.Arg518Trp)/c.1552C > T(p.Arg518Trp)

^aPatients included in previously reported NPC Registry baseline characteristics study [19]; ^bPatients included in previously reported NPC Registry baseline and longitudinal data study [19, 20]; ^cpatient died; ^dsecond mutant allele not found after full genome sequencing. ‘–’, no data/not known; C cataplexy, E epilepsy, FA foetal ascites, Gx gastrostomy, HM hepatomegaly, HS/S hepatosplenomegaly/splenomegaly, LD liver disease, LTx liver transplant, m months, NC neonatal cholestasis, PJ prolonged jaundice, PM post mortem, y years, w weeks

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