Table 2.

Sociodemographic, biochemical, enzymatic, genetic and clinical information on 88 patients with MCC deficiency 18 individuals identified by selective metabolic screening due to clinical symptoms (n = 17, no clinical details in n = 1)

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		Allele 1 Allele 2
30	m	Turkish	newborn	died at 33 days	++	++	++	0	637	MCCC2	c.1574+1G>A c.1574+1G>A	(p.F497Gfs*4) (p.F497Gfs*4)	acute decompensation on first day of life, acidosis, hypoglycaemia, hyperlactemia, hyperammonemia, encephalopathy, depressed neonatal reflexes, hypertonic episodes, prominent hypotonia, respiratory insufficiency requiring assisted ventilation, cardiac arrest, patient deceased on day 33
													CT scan of the brain: multiple cysts, ventricular dilatation, cerebral atrophy
32a	m	Arab	4 years	14	++	++	++	5.0	863	MCCC2	c.127C>T c.127C>T	p.Q43* p.Q43*	muscular hypotonia, weakness, mild motor delay (fr)
35a	m	Caucasian	9 months	16	na	++	++	7.3	976	MCCC2	(exon 7 to 14 skipping) (exon 7 to 14 skipping)	(p.I209Pfs*43) (p.I209Pfs*43)	developmental delay, familial nystagmus, hyperopia, significant hand tremor, mild learning disability, failure to thrive, unpleasant odour descibed as "smelling like cat`s urine", hypothermia, ketonuria, hypoglycemia and mild hyperammonemia prior to stabilisation on dietary therapy (ltf, 3y)
36	f	Turkish	3 years	11	++	++	++	0.4	420	MCCC1	c.1527C>A c.1527C>A	p.C509* p.C509*	mental and speech retardation, spasticity, impaired physical performance (ltf)
42	f	Caucasian	?	24	++	++	++	0	664	MCCC2	c.929C>G c.929C>G	p.P310R p.P310R	severe muscular weakness, muscle pain (ltf, 16y)
44	m	Caucasian	1.5 years	10	na	++	++	4.0	425	MCCC2	c.463C>T c.463C>T	p.R155W p.R155W	psychomotor retardation, seizures, muscular hypotonia, metabolic stroke, failure to thrive, clinodactyly of the 5th fingers (fr)
50	f	Arab	13 years	21	na	++	++	8.1	761	MCCC1	c.1882G>T c.1114C>T	p.E628* p.Q372*	mild Reye-like episode and encephalitis during Influenza A infection at age 5 years, mild learning disability, severe attention-deficit hyperactivity disorder, multiple sclerosis (fr)
54	m	Asian	?	13	++	++	++	1.3	1162	MCCC1	c.980C>G c.639+2T>A	p.S327* p.S164Rfs*3	psychomotor retardation, attention deficit hyperactivity disorder, frequent skin picking behaviour (ltf)
60	f	Turkish	?	10	++	++	++	6.4	754	MCCC1	c.2079delA c.2079delA	p.V694* p.V694*	mild global psychomotor retardation, convulsions starting at the age of 18 months during febrile episode, continued as generalized tonic clonic seizures after the age of 3 years, nephrolithiasis, episodes of hematuria (ltf, 4 y)
63	m	Turkish	?	8	++	++	na	12.0	729	MCCC2	c.464G>A c.464G>A	p.R155Q p.R155Q	3 metabolic decompensations with encephalopathy, seizures, acidosis, hypoglycemia, mild developmental retardation
68	m	Turkish	3 years	9	++	++	++	2.4	335	MCCC1	c.1155A>C c.1155A>C	R385S R385S	severe metabolic decompensation with metabolic stroke, cerebral edema and hemiparesis, mild psychomotor retardation, seizures (fr)
77	m	Arab	8 months	9	na	++	++	0	777	MCCC2	c.463C>T c.463C>T	p.R155W p.R155W	psychomotor and speech retardation, kyphoscolisis, genu varum, hypogammaglobulinemia, chronic diarrhea, reversible cytopenia under TPN (ltf, 7y)
80	m	Turkish	1.5 years	9	++	++	n (6m)++ (1y)	22.8	1162	MCCC2	c.116C>T c.116C>T	p.S39F p.S39F	speech retardation, seizures, recurring attacks of status epilepticus (ltf, 3y)
89	f	Caucasian	7 months	10	na	na	na	17.0	986	MCCC2	(exon 8 to 10 skipping)	(p.K248_V334del)	failure to thrive, poor feeding (ltf, 5y)
											(exon 8 to 10 skipping)	(p.K248_V334del)
92	m	Caucasian	1 week	5	++	++	++	na	na	MCCC2	c.710G>A c.1149+5G>C	p.G237D p.?	acute metabolic crisis, mild retardation (fr)
96a	m	Turkish	1 year	6	++	++	++	7.3	1212	MCCC1	c.873+ 4524_6787del2264	large deletion	acidosis at 1 year of age, atonic seizures starting at 1 year of age (fr)
											c.873+ 4524_6787del2264	large deletion
99a	f	Turkish	8 years	died at 8 years	++	++	++	na	na	MCCC2	c.392G>T c.392G>T	p.C131F p.C131F	catecholaminergic ventricular tachycardia (mutation in RyR2 gene) sudden cardiac death at age 8 years
69	?	Arab	?	9	na	na	na	18.9	1210	MCCC2	c.1567A>G	p.S523G	?
											c.1567A>G	p.S523G

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.