Mudd’s disease (MAT I/III deficiency): a survey of data for MAT1A homozygotes and compound heterozygotes

Chien, Yin-Hsiu; Abdenur, Jose E.; Baronio, Federico; Bannick, Allison Anne; Corrales, Fernando; Couce, Maria; Donner, Markus G.; Ficicioglu, Can; Freehauf, Cynthia; Frithiof, Deborah; Gotway, Garrett; Hirabayashi, Koichi; Hofstede, Floris; Hoganson, George; Hwu, Wuh-Liang; James, Philip; Kim, Sook; Korman, Stanley H.; Lachmann, Robin; Levy, Harvey; Lindner, Martin; Lykopoulou, Lilia; Mayatepek, Ertan; Muntau, Ania; Okano, Yoshiyuki; Raymond, Kimiyo; Rubio-Gozalbo, Estela; Scholl-Bürgi, Sabine; Schulze, Andreas; Singh, Rani; Stabler, Sally; Stuy, Mary; Thomas, Janet; Wagner, Conrad; Wilson, William G.; Wortmann, Saskia; Yamamoto, Shigenori; Pao, Maryland; Blom, Henk J.

doi:10.1186/s13023-015-0321-y

Orphanet Journal of Rare Diseases

Table 2 Patients with evidence of CNS abnormalities

From: Mudd’s disease (MAT I/III deficiency): a survey of data for MAT1A homozygotes and compound heterozygotes

Patient	Sex	Age last report years	MAT1A allele 1/allele 2	MAT activity % of WT	Cause ascer- tain-ment	Age < 5 m Met range	Age ≥ 5 m Met mean ± SD	MRI (age done) Other	Citation^†
1	M	24.2	c.113G>A (p.Ser38Asp)	8*	NBS	670–1237	1030	Abnormal (20.7)	[14, 16, 27, 58]
1	M	24.2	c.255delCA (p.Tyr92X)	0/NA	670	670–1237	1030	Abnormal (20.7)	[14, 16, 27, 58]
4	F	32	c.827insG (p.Lys351X)	NA	NBS	---	600–1400	Abnormal (11)	[26, 64]
4	F	32	c.827insG (p.Lys351X)	NA	NBS	---	600–1400	Normal (12)	[26, 64]
5	F	26.1	c.791C>T (p.Arg264Cys)	0.3/23	NBS	201–1740	909 ± 272	Normal (13)	[27, 47, 58]
			c.1006G>A (p.Gly336Arg)		201			IQ 84 (14)
			c.1006G>A (p.Gly336Arg)		201			Learning disability (14)
7	M	17.8	c.292G>A (splicing)	NA	NBS	1226–1664	1428 ± 320	Normal (0.75)	[27, 58]
			c.292G>A (splicing)		1226			Abnormal (4.2)
			c.292G>A (splicing)		1226			Abnormal (11)
8	F	13.6	c.1043delTG (p.His350X)	NA	Dystonia	---	1157 ± 445	Abnormal (9)	[26, 58]
8	F	13.6	c.1043delTG (p.His350X)	NA	Dystonia	---	1157 ± 445	Abnormal (9)	[26, 58]
9	M	8.7	c.595C>T (p.Arg199Cys)	11/NA	NBS	966–1467	879 ± 140	Normal (6)	[26, 58]
9	M	8.7	c.539insTG (p.Thr185X)	11/NA	NBS	966–1467	879 ± 140	IQ 65 (6)	[26, 58]
13	F	6.2	c.595C>T (p.Arg199Cys)	11/11	NBS	635–738	485 ± 49	Abnormal (8)	[26, 58]
13	F	6.2	c.595C>T (p.Arg199Cys)	11/11	NBS	635–738	485 ± 49	Slow at school (16)	[26, 58]
20	F	10.8	c.205G>A (p.Gly69Ser)	109/NA	NBS	---	1400	Abnormal (10)	[42]
20	F	10.8	c.1188G>T (p.X396YfsX464)	109/NA	1560	---	1400	Abnormal (10)	[42]
22	F	7.5	c.874C>T (p.Arg292Cys)	14/NA	NBS	---	1005–1676	Abnormal (2.9)	[38, 81]
			c.1067G>T (p.Arg356Leu)		395			Normal (6.4)
			c.1067G>T (p.Arg356Leu)		395			IQ 60 (5.4)
29	M	14.2	c.125T>C (p.Leu42Pro)	10/10	NBS	121–1541	1437 ± 498	Abnormal (13)	[34, 37, 44]
29	M	14.2	c.125T>C (p.Leu42Pro)	10/10	121	121–1541	1437 ± 498	IQ 73 (13)	[34, 37, 44]
30^e	M	7.0	c.274T>C (p.Tyr92His)	104/11	NBS	740	830 ± 368	IQ 121 (3)	[34, 36, 41]
			c.1067G>C (p.Arg356Pro)					Abnormal (3.8)
								Better (5.5)
								Normal (7)
31^e	M	3	c.274T>C (p.Tyr92His)	104/11	NBS	820–2250	900–1140	Abnormal (0.8)	[34, 41]
31^e	M	3	c.1067G>C (p.Arg356Pro)	104/11	NBS	820–2250	900–1140	Abnormal (3)	[34, 41]
32	M	9.4	c.433G>A (p.Glu145Lys)	NA/14	NBS	1740–1870	740–1150	Abnormal (5)	[34, 43]
			c.874C>T (p.Arg292Cys)					Abnormal (9.4)
								IQ 108 (9.4)
34	M	0.63	c.1068G>A (p.Arg356Trp)	4/4	NA	1846–3500	---	Severe retarded	[34]
34	M	0.63	c.1068G>A (p.Arg356Trp)	4/4	NA	1846–3500	---	Severe retarded	[34]
35	F	2.8	c.292G>A (splicing)	NA/11	NBS	1544–1685	1159	Abnormal (1.2)	[26]
35	F	2.8	c.595C>T (p.Arg199Cys)	NA/11	NBS	1544–1685	1159	Better (1.8)	[26]
36^f	F	1.3	c.539insTG (p.Thr185X)	NA/20	NBS†	1400	1549	Normal (2.3)	[34]
36^f	F	1.3	c.890C>A (p.Ala297Asp)	NA/20	1400	1400	1549	Delayed development (2.3)	[34]
37^f	F	1.3	c.539insTG (p.Thr185X)	NA/20	NBS† 1400	1400–1421	1614	Delayed development (2.3)	[34]
37^f	F	1.3	c.890C>A (p.Ala297Asp)	NA/20	NBS† 1400	1400–1421	1614	Delayed development (2.3)	[34]
38^g	F	13	c.896G>A (p.Arg299His)	13/13	Neuro-logical	--	1016 ± 549	Abnormal (12.8)	[34]
38^g	F	13	c.896G>A (p.Arg299His)	13/13	Neuro-logical	--	1016 ± 549	Delayed development (3)	[34]
39^g	M	9.8	c.896G>A (p.Arg299His)	13/13	Family	---	1000 ± 192	Abnormal (5.2)	[34]
39^g	M	9.8	c.896G>A (p.Arg299His)	13/13	Family	---	1000 ± 192	Delayed in learning (10.5)	[34]
41	F	7.6	p.MAT1Adel	NA	NBS	192–1608	---	Abnormal (0.2)
41	F	7.6	p.MAT1Adel	NA	192	192–1608	---	Normal (7.1)
42	M	1.9	c.607delATC (p.Ile203del)	NA	NBS	148–1490	1144 ± 143	Abnormal (1.2)
42	M	1.9	c.607delATC (p.Ile203del)	NA	148	148–1490	1144 ± 143	Speech delay (1.5)
43	M	4.2	c.934C>T (p.Arg312Trp)	NA	NBS	460–1437	1120	Abnormal (3.8)
43	M	4.2	c.934C>T (p.Arg312Trp)	NA	NBS	460–1437	1120	IQ 78 (3.3)
45	F	4.5	c.292G>C (p.Gly98Arg, splicing?)	NA	NBS	507–1012	901 ± 163	Abnormal (4)
45	F	4.5	c.292G>C (p.Gly98Arg, splicing?)	NA	NBS	507–1012	901 ± 163	Better (4.5)
46	F	34	c.274T>C (p.Tyr92His)	8.3*	NBS	402–1340	1326 ± 159	Abnormal (30)	[15]
46	F	34	c.1067G>C (p.Arg356Pro)	104/11	NBS	402–1340	1326 ± 159	IQ 99 (9)	[15]
47	F	17	c.1033insG (p.Lys351X)	NA	Unknown	---	---	Abnormal (9)
47	F	17	c.1033insG (p.Lys351X)	NA	Unknown	---	---	Almost normal (17)
50^h	F	4.9	c.896G>A (p.Arg299His)	NA	Neuro-logical	---	878 ± 136	Abnormal (3.3)	[34]
50^h	F	4.9	c.896G>A (p.Arg299His)	NA	Neuro-logical	---	878 ± 136	Abnormal (3.3)	[34]
51^h	F	4.7	c.896G>A (p.Arg299His)	NA	Family	---	641 ± 74	Behavior deterioration (3.7)	[34]
51^h	F	4.7	c.896G>A (p.Arg299His)	NA	Family	---	641 ± 74	Behavior deterioration (3.7)	[34]
56	F	39	c.896G>A (p.Arg299His)	NA	Hi met baby	---	1233 ± 513	Neurological abnormality
56	F	39	c.896G>A (p.Arg299His)	NA	Hi met baby	---	1233 ± 513	Neurological abnormality
60	F	6.1	c.895C>T (p.Arg299Cys)	20/20	NBS	800–1067	1013 ± 283	Abnormal (1.4)	[34, 40]
60	F	6.1	c.895C>T (p.Arg299Cys)	20/20	NBS	800–1067	1013 ± 283	Mild delay (5.6)	[34, 40]
61	F	1.0	c.688G>A (p.Val230Met)	NA /11	NBS	205–328	84 ± 34	Abnormal (4.5)	[82]
61	F	1.0	c.1067G>C (p.Arg356Pro)	NA /11	NBS	205–328	84 ± 34	Neurologic normal (5.5)	[82]
62	M	4.3	c.169G>A (p.Glu57Lys, splicing?)	NA	NBS	461	812 ± 309	Developmental delay (2.3)
								MRI normal (2.3)
								Development normal (4.3)
63	M	2.9	c.169-2A>c.734_735delAG (p.Gln245Profs*20)G	NA/0.3	NBS	938–1271	905 ± 99	Abnormal (0.8)
63	M	2.9	c.791C>T (p.Arg264Cys)	NA/0.3	NBS	938–1271	905 ± 99	Worsen (1.5)

^†Patients are assigned the same identifiers as were used when they were first described in the following papers: patient 1 [14, 16]; patients 5, 7, 8, 9 and 13 [58]; patient 20: 14 [42]; patient 22 [38]; patient 29: patient 2 [44]; patient 30 [36]; patient 31 [41]; patient 32 [43]; patient 46: case 2 [15], and patient 61 [82]
*Activity based on assay of hepatic extract; others based on activity of mutant recombinant forms expressed in E coli [34]
^a Sibs are designated by the same superscript
^†Cont. indicates that methionine restriction or AdoMet supplementation was continuing at last report
NBS: Newborn screening
NA: not available
Met: methionine concentration in umol/L

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ISSN: 1750-1172

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