成人脑型肾上腺脑白质营养不良的临床及遗传学特征

刘桃桃, 刘晓黎, 邬静莹, 倪瑞隆, 张梦圆, 季杜欣, 张梅, 曹立

Clinical and genetic characteristics of adult cerebral adrenoleukodystrophy

LIU Taotao, LIU Xiaoli, WU Jingying, NI Ruilong, ZHANG Mengyuan, JI Duxin, ZHANG Mei, CAO Li

表1 ACALD患者基本信息、临床特征及实验室指标

Tab 1 General information， and clinical and biochemical characteristics of ACALD patients

Items	P1	P2	P3	P4	P5	P6	P7	P8
Age of onset/Years	27	23	40	37	34	30	33	38
Disease duration/Months	12	4	59	31	5	4	8	16
First symptoms	Memory and cognitive decline	Dizziness with occipital numbness, insomnia	Mental and behavioral abnormalities	Dysarthria and ataxia	Bad temper, personality change	Memory and cognitive decline	Memory decline	Bad temper, personality change
MMSE/MoCA	21/17	ND	NA	ND	21/16	14/9	23/16	NA
VLCFA
C26(≤1.30 nmol/mL)	5.71	ND	3.94	ND	3.77	3.03	3.28	3.38
C24/C22(≤1.39)	1.89	ND	1.50	ND	1.46	1.77	1.76	1.95
C26/C22(≤0.023)	0.132	ND	0.065	ND	0.077	0.068	0.070	0.073
Adrenal insufficiency
Cortisol levels	↓	ND	↓	↓	N	N	↓	↓
ACTH	↑	ND	↑	↑	N	↑	↑	↑
Protein content in cerebrospinal fluid	1.00 g/L	N	0.47 g/L	0.47 g/L	N	ND	ND	ND
Mutation information
Exon	8	10	6	7	1	1	6	3
Nucleotide mutations	c.1817C>T	c.2135G>A	c.1559T>C	c.1750delC	c.323C>T	c.160_170delACGCAGGAGGC	c.1534G>A	c.1202G>A
Amino acid variants	S606L	R712H	L520P	H584Tfs*52	S108L	T54Lfs*137	G512S	R401Q
ACMG	Pathogenic	VUS	VUS	Pathogenic	Pathogenic	Pathogenic	Pathogenic	Pathogenic
Reported phenotypes	CCALD^[3],AMN^[4],AO^[5]	NB^[6]	NB^[6]	‒	CCALD^[7],AO^[8], AMN^[9], Olivo-ponto-cerebellar^[10]	‒	CCALD^[11],AMN^[12],ACALD^[11],AO^[13],Female^[14]	CCALD^[7],AMN^[15],ACALD^[16],NB^[6]AO^[17], Female carrier^[18]