. 2014 Mar 6;94(3):453–461. doi: 10.1016/j.ajhg.2014.01.006

Table 1.

Overview of Biochemical Abnormalities Resulting from CA-VA Deficiency: In Theory and for the Index Cases for Families 1, 2, and 3

Theoretical Possibilities		Actual Results^a
Possible Enzyme Deficiency	Predicted Secondary Biochemical Abnormalities	Metabolite	Family 1			Family 2		Family 3
Possible Enzyme Deficiency	Predicted Secondary Biochemical Abnormalities	Metabolite	Female	Male	Normal^b	Male	Normal	Male	Normal
carbamoyl phosphate synthetase	↑ ammonia	plasma ammonia (μM)	780^∗	238^∗	<40	422^∗	<50	258^∗	<40
	↓ citrulline	plasma citrulline (μM)	5^∗	18	8–47	17	3–36		10–45
	↓ arginine	plasma arginine (μM)	17^∗	NA	32–142	35	17–119	22	12–133
	↑ glutamine	plasma glutamine (μM)	1,051^∗	1,237^∗	457–746	2,606^∗	243–822	571	254–823
	N ornithine	plasma ornithine (μM)	15^∗	82	27–207	146	38–272	17	15–200
	N orotate	urine orotate	non-det	1.9	<4.3	2.2	<4.9	0.4	<3
pyruvate carboxylase	↓ gluconeogenesis (hypoglycemia)	serum glucose (mm)	2.2^∗	2.9^∗	3.3–7.0	2.9^∗	3.0–8.0	3.2^∗	3.5–6.0
		serum lactate (mm)	9.1^∗	8.8^∗	0.5–2.2	8.1^∗	1.0–1.8	5.6^∗	0.6–2.6
		plasma alanine (μm)	1,531^∗	609^∗	148–475	1,078^∗	132–455	603^∗	143–439
	redox imbalance (↑ lactate & dicarboxylic acids)	plasma proline (μm)	418^∗	371^∗	40–332	625^∗	78–523	283^∗	52–298
	↓ tricyclic acid cycle intermediates (cataplerosis)	urine lactate	3,737^∗	4,109^∗	<200	28,000^∗	<456	grossly increased^∗
		urine 3-OH-butryric acid	7,902^∗	2,657^∗	<21	7,060^∗	<22	grossly increased^∗
		urine aceto-acetic acid	584^∗	927^∗	non-det	++^c		grossly increased^∗
		urine fumaric acid	13.8^∗	38.5^∗	<10	8	<13	moderately increased
		urine 2-α-ketoglutaric acid	143^∗	254.6^∗	<112	300^∗	<267	slightly increased^∗
		urine adipic acid	55^∗	219.8^∗	<29	340	<25	normal
		urine suberic acid	18.6^∗	48.6^∗	<13	29	<15	normal
		urine sebacic acid	NA	18.7^∗	<10	NA		normal
	↑ lysine	plasma lysine (μm)	87	161	71–272	306	71–272	94	71–272
proprionyl-CoA carboxylase	↑ 3-OH-propionic acid	urine 3-OH-propionic acid	79.38^∗	54.57^∗	<16	59^∗	<21	normal
	↑ propionylglycine	urine proprionylglycine	1.29^∗	3.28^∗	non-det	5.6^∗	<2	trace^∗
	↑ methylcitrate	urine methylcitrate	6.4^∗	non-det	non-det	normal^c		trace^∗
3-methylcrotonyl-CoA carboxylase	↑ 3methylcrotonylglycine	urine 3-methylcrotonylglycine	22.9^∗	non-det	<10	17^∗	<5	trace^∗
	↑ 3OH-isovaleric acid	urine 3-OH-isovaleric acid	40.13^∗	55.50^∗	<38	327^∗	<55	increased^∗

All values in urine are expressed as μmol/mmol of creatinine. Abbreviations are as follows: N, normal (within reference range); NA, not available; non-det, nondetectable.

In each individual, the value with maximal deviation from normal during crisis is provided. Asterisks (^∗) indicate abnormal values.

Normal values differ for each family studied because values were measured in different laboratories.

Qualitative assessment.