3-methylcrotonyl-CoA carboxylase deficiency: Clinical, biochemical, enzymatic and molecular studies in 88 individuals

Table 4 Sociodemographic, biochemical, enzymatic, genetic and clinical information on 88 patients with MCC deficiency Mothers identified following the positive newborn screening result of their offspring (n = 9)

Pt #	Sex	Ethnic origin	Age at diagnosis	Current age (y)	Biochemical phenotype			Carboxylase activities in fibroblasts (pmol/min/mg protein)¹		Genotype			Clinical phenotype^§
					DBS/ plasma	urine				affected gene	Nucleotide change (at RNA level)	Amino acid change (predicted from RNA)
					C5OH	3-HIVA	3MCG	MCC	PCC	affected gene	Allele 1 Allele 2	Amino acid change (predicted from RNA)
37	f	Asian	32 years	40	++	++	++	9.6	1268	MCCC2	c.1367C>T	p.A456V	asymptomatic (ltf)
											c.1367C>T	p.A456V
51	f	Asian	24 years	32	++	na	na	0	475	MCCC2	c.351_353delTGG◊ -	p.G118del -	asymptomatic (ltf)
73c	f	Faroe Islands	29 years	37	++	++	++	na	na	MCCC1	c.1526delG	p.C509Sfs*14	asymptomatic (fr)
											c.1526delG	p.C509Sfs*14
83	f	Caucasian	?	38	++	++	++	na	na	MCCC1	c.539G>T	p.G180V	asymptomatic (fr)
											c.558delA	p.Q186Hfs*6
85	f	Caucasian	38 years	49	++	+	n	na	na	MCCC2	c.517dupT	p.S173Ffs*25	asymptomatic (ltf)
											c.599T>A	p.I200N
100	f	Caucasian	29 years	34	++	++	++	na	na	MCCC2	c.505T>G	p.Y169D	asymptomatic (fr)
											c.1073-12C>G
											(r.1073_1216del+ r.1073insr.1073- 48_r.1073-1)	(p.G358Vfs6+ p.G358Afs12)
66	f	Caucasian	34 years	41	+	+	++	10.0	807	MCCC2	c.436T>Ac.416_427del12ins16	p.Y146Np.T139_G143> RWVPGEfs*35	several metabolic crises with hypoglycemia during febrile illnesses, metabolic stroke, cardiomopathy, paraesthesias (ltf)
87	f	Faroe Islands	28 years	33	++	n	n	13.0	826	MCCC1	c.1526delGc.1526delG	p.C509Sfs14p.C509Sfs14	chronic tiredness (fr), otherwise asymptomatic
33	f	Turkish	36 years	45	++	++	++	4.6	520	MCCC2	c.282-1G>C	p.S95_G128del	?
											c.282-1G>C	p.S95_G128del

¹ control values measured in 53 cell lines, expressed as median value and (range): MCC activity, 305 pmol/min/mg protein (134-671); PCC activity, 583 (208-1165); ratio of PCC/MCC activity, 1.93 (1.19 – 2.58).
§ information in brackets: fr followed regularly, ltf lost to follow-up, age of last follow-up, if known.
+ slightly elevated.
++ massively elevated; C5OH 3-hydroxyisovalerylcarnitine; DBS dried blood spots; 3-HIVA 3-hydroxyisovaleric acid; 3-MCG 3-methylcrotonylglycine; f female; fr followed regularly; ltf lost to follow-up; m male; MCC methylcrotonyl-CoA carboxylase
n normal; na not available; NBS newborn screening; PCC propionyl-CoA carboxylase; Pt # Patient number; RNA nd RNA not detectable; SMS selective metabolic screening; y years
^◊ mutation heterozygous on genomic PCR, homozygous in RT-PCR; ^# diagnosed following the positive NBS result of their baby; ? not known.

ISSN: 1750-1172