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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)

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

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. 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).
  2. § 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.