Table 3.

Laboratory markers for newborn screening of homocystinurias and methylation defects in R4S

Disease	Marker	Healthy newborns-concentration in DBS				Patients-concentration in DBS						Recommended range for cut-off value	Comment
		Number of laboratories with data	1 %	median	99 %	Number of patients	1 %	5 %	median	90 %	99 %
CBS deficiency	Met (μmol/L)	154	10.65	20	39	124	26	51	103	540	964	>39–50	possibly poor sensitivity for pyridoxine-responsive form
	Met/Phe	92	0.23	0.41	0.75	107	0.55	0.97	2.17	11.50	25	>0.75–0.97
	tHcy (μmol/L)	3	4.12	6.00	10.70	31	12.46	14.2	40	80	158	>0.7–12.4
	Low Met/tHcy	2	2.24	5.10	12.08	29	0.86	0.93	2.24	4.29	5.75	<4.00–5.00
cblC/cblD	C3 acylcarnitine (μmol/L)	151	0.58	1.68	4.3	198	2.65	3.46	8.40	13.3	19	>4.3–5.4	poor sensitivity
	C3/C2 acylcarnitine	136	0.036	0.08	0.18	187	0.13	0.20	0.39	0.62	1.67	>0.18–0.20
	MMA (μmol/L)	3	0.010	0.20	1.52	28	7.13	10.94	28	114	437	>3.0–7.0
	Methylcitrate (μmol/L)	2	0.036	0.21	12.4	10	0.37	0.38	0.63	6.13	10.42	>0.7–1.2
	Met (μmol/L)	154	10.65	20	39		3.62	4.90	10.2	26	47	<10.2–10.6	poor sensitivity
	Low Met/Phe	92	0.23	0.41	0.75	178	0.050	0.081	0.18	0.47	0.70	<0.17–0.23	poor sensitivity
	tHcy (μmol/L)	3	4.12	6.00	10.70	23	14.66	20	52.00	172	241	>10.7–12.4
cblF	C3 acylcarnitine (μmol/L)	151	0.58	1.68	4.3	4	8.75	8.88	10.18	12.87	13.76	>4.3–5.4
cbE/cblG/ MTHFR	Low Met (μmol/L)	154	10.65	20	39	17	2.52	3.78	5.91	9.76	10.22	<10.2–10.6
	Low Met/Phe	92	0.23	0.41	0.75	17	0.038	0.068	0.10	0.16	0.17	<0.17–0.23
	tHcy (μmol/L)	3	4.12	6.00	10.70	8	42	48	70	132	154	>10.7–12.4
	Low Met/tHcy	2	2.24	5.10	12.08	8	0.034	0.048	0.083	0.17	0.25	<4.00–5.00
MATI/III	Met (μmol/L)	154	10.65	20	39	143	44	50	103	173	582	>39–50
	Met/Phe	92	0.23	0.41	0.75	137	0.84	1.1	1.77	3.72	6.32	>0.75–0.97
	Met/tHcy	2	2.24	5.10	12.08	2	10.87	12.53	31	48	52	>14.00–15.00