Clinical feature and outcome of late-onset cobalamin C disease patients with neuropsychiatric presentations: a Chinese case series

Figures & data

Table 1 Clinical manifestations of 26 patients with late-onset cblC disease

No.	Sex	Age at diagnosis/onset year		Clinical Cognitive deficit	Presentations
			Psychiatric changes		Limb weakness	Seizures	Abnormal gait	Others	Anemia
1	M	10/9	−	−	−	−	+	−	+
2	F	14/14	−	−	+	−	+	−	−
3	M	13/13	−	−	+	−	−	−	−
4	M	16/15	+	−	−	+	+	−	−
5	F	19/18	+	+	−	−	+	−	−
6	F	22/20	+	−	−	−	−	−	−
7	F	31/24	+	−	+	−	−	−	−
8	F	15/13	−	−	+	−	−	−	−
9	F	16/16	+	−	−	−	+	−	−
10	F	5/4	−	−	+	+	−	−	+
11	F	11/7	−	+	+	+	−	−	−
12	F	14/14	−	+	−	−	+	−	−
13	M	18/7	+	+	−	−	−	Renal dysfunction	+
14	F	20/19	+	+	−	−	−	Renal dysfunction	+
15	M	14/12	−	+	−	+	−	−	+
16	F	24/14	+	−	−	−	−	Pulmonary embolism	+
17	M	16/12	−	−	+	+	+	−	−
18	M	14/10	−	−	+	-	−	−	−
19	M	39/38	−	−	+	−	+	−	−
20	F	15/15	+	−	+	−	−	−	−
21	M	29/29	−	−	−	−	+	−	−
22	M	20/18	+	−	+	−	−	−	−
23	M	29/19	−	+	+	-	+	−	−
24	F	22/17	−	−	+	-	+	−	+
25	F	18/18	+	−	−	+	−	−	−
26	M	29/29	+	−	−	+	−	−	−

Abbreviations: +, positive result; −, negative result; cblC, cobalamin C; F, female; M, male.

Table 2 Accessory examinations and gene mutations of 26 patients with late-onset cblC disease

No.	Serum Hcy (μmol/L)	Urine MMA (μmol/L)	C3/C2	MMACHC gene mutations (amino acid substitutions)	EMG	X-ray scoliosis
1	102	89.2	0.62	c.217C>T (p.R73^*), c.615C>A (p.Y205*)	Mild peripheral nerve damage	+
2	69.5	54.5	0.59	c.354G>C (p.Q118H), c.570_571insT (p.A191Cfs^*12)	Mild peripheral nerve damage	+
3	62.8	198	0.97	c.567dupT (p.1190Yfs^* 13), c.482G>A (p.R161Q)	ND	+
4	110.1	101.9	0.64	c.482G>A (p.R161Q), c.609G>A (p.W203^*)	Normal	+
5	69.5	52.6	0.48	c.445_446del (p.C149Lfs^*16), c.482G>A (p.R161Q)	Peripheral nerve damage	+
6	128	103.2	0.56	c.609G>A (p.W203^*), c.365A>G (p.H122R)	ND	−
7	75.4	91.9	0.53	c463G>C (p.G155R), c.609G>A (p.W203^*)	Peripheral nerve damage	+
8	111.8	141.9	0.34	c.482G>A (p.R161Q), c.427C>T (p.Q143^*)	Normal	+
9	120.4	140.9	0.60	c.482G>A (p.R161Q), c.609G>A (p.W203^*)	Mild peripheral nerve damage	+
10	109	105.2	0.35	c.609G>A (p.W203^*), c.609G>A (p.W203^*)	ND	+
11	103.3	236.5	0.68	c.609G>A (p.W203^*), c.609G>A (p.W203^*)	Peripheral nerve damage	+
12	77.2	31	0.52	c.609G>A (p.W203^*), c.482G>A (p.R161Q)	ND	−
13	127.6	97	0.58	c.452A>G (p.H151A), c.452A>G (p.H151A)	ND	+
14	115.2	178	0.72	c.452A>G (p.H151A), c.452A>G (p.H151A)	Peripheral nerve damage	+
15	146.3	116	1.03	c.1A>G (p.M1?), c.615C>A (p.Y205^*)	Peripheral nerve damage	−
16	114	111.7	0.96	c.482G>A (p.R161Q), c.656_658del (p.K220Rfs^*71)	ND	+
17	98	130	0.49	c.482G>A (p.R161Q), c.657_659del (p.K220Rfs^*71)	Normal	+
18	61.4	37.4	0.44	c.482G>A (p.R161Q), c.609G>A (p.W203^*)	Mild peripheral nerve damage	ND
19	67.1	34.9	0.36	c.80A>G (p.Q27R), c.609G>A (p.W203^*)	Mild peripheral nerve damage	+
20	62.3	82.4	0.51	c.482G>A (p.R161Q), c.609G>A (p.W203^*)	ND	+
21	102.8	141.6	0.69	c.482G>A (p.R161Q), c.656_658del (p.K220Rfs^*71)	Peripheral nerve damage	+
22	193.4	59.3	0.56	c.482G>A (p.R161Q), c.656_658del (p.K220Rfs^*71)	Peripheral nerve damage	+
23	114.2	229.1	0.59	c.482G>A (p.R161Q), c.658_660del (p.A221Gfs^*71)	Peripheral nerve damage	ND
24	57.5	43.6	0.62	c.482G>A (p.R161Q), c.658_660del (p.A221Gfs^*71)	Mild peripheral nerve damage	ND
25	273.3	65.7	0.56	c.1A>G (p.M1?), c.445_446del (p.C149Lfs^*16)	Mild peripheral nerve damage	ND
26	103.3	120.1	0.89	c.482G>A (p.R161Q), c.567dupT (p.1190Yfs^*13)	ND	ND

Abbreviations: +, positive result; −, negative result; cblC, cobalamin C; EMG, electromyographic; F, female; Hcy, homocysteine; M, male; MMA, methylmalonic acid; MMACHC, methylmalonic aciduria and homocystinuria type C protein; ND, not done or no date available.

Table 3 Treatment and outcome of 26 patients with late-onset cblC disease

No.	Brain MRI	Spine MRI	Main treatment drugs			mRS
			Cobalamin	Betaine	Folate	Before/after treatments
1	Cerebellum atrophy	Cervical and thoracic cord atrophy	+	+	+	2/1
2	Normal	Thoracic cord atrophy	+	+	+	2/1
3	Normal	Thoracic cord atrophy	+	+	+	2/1
4	Normal	LETM (cervical cord)	+	+	+	3/1
5	Hyperintensity of basal ganglia and cerebellum	Thoracic cord atrophy	+	+	+	2/1
6	Normal	Normal	+	+	+	2/1
7	Normal	LETM (cervical cord)	+	+	+	3/1
8	Normal	Thoracic cord atrophy	+	+	+	2/1
9	Cerebral cortical atrophy	ND	+	+	+	3/1
10	Cerebral cortical atrophy; white matter demyelination	ND	+	+	+	2/1
11	Hydrocephalus	ND	+	+	+	2/1
12	Cerebellum atrophy	ND	+	+	+	2/1
13	Cerebral cortical atrophy	ND	+	+	+	3/2
14	Cerebral cortical atrophy	Cervical and thoracic cord atrophy	+	+	−	3/1
15	RPLS	ND	+	+	+	2/1
16	Cerebral cortical atrophy	Thoracic cord atrophy	+	+	−	3/1
17	Normal	Thoracic cord atrophy	+	+	+	3/2
18	Normal	Thoracic cord atrophy	+	+	−	3/1
19	Normal	LETM	+	+	−	2/1
20	Normal	ND	+	+	+	2/1
21	ND	Normal	+	+	+	2/1
22	Cerebral cortical atrophy	Thoracic cord atrophy	+	+	−	2/1
23	Cerebral cortical atrophy	Thoracic cord atrophy	+	+	+	3/2
24	Cerebral white matter demyelination	LETM	+	+	−	3/2
25	Normal	ND	+	+	+	3/1
26	Normal	ND	+	+	+	2/1

Abbreviations: +, Positive result; −, Negative result; cblC, Cobalamin C; LETM, longitudinally extensive transverse myelitis; mRS, modified Rankin Scale; ND, Not done or no date available; RPLS, reversible posterior leukoencephalopathy syndrome.