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 | ||||||||||||