Table 1.
Clinical and Biochemical Features of Male Subjects with HCFC1 Variants
| Subject | Age of Onset | Clinical Symptoms | Genetic Testing (Negative) | HCFC1 Variant | Plasma tHcya(μmol/l) | Serum MMAb(μmol/l) | Urine MMAc(mmol/mol creatinine) |
|---|---|---|---|---|---|---|---|
| 1 | 4 months | severe developmental delay, infantile spasms with hypsarrythmia, gyral cortical malformation, microcephaly, chorea, undescended testes, megacolon | MMACHC | c.344C>Td (p.Ala115Val) | 141 | 21.5 | ND |
| 2 | 4 months | severe developmental delay, intractable epilepsy, choreoathetosis, microcephaly, FTT | MMACHC | c.344C>T (p.Ala115Val) | ND | ND | 650 |
| 3 | prenatal | severe developmental delay, neonatal epilepsy, choreoathetosis, congenital microcephaly, FTT | MMACHC | c.344C>T (p.Ala115Val) | ND | ND | elevated |
| 4 | <3 months | infantile spasms with hypsarrythmia, absent development | MMACHC | c.344C>T (p.Ala115Val) | 5 | ND | 201 |
| 5 | 2 months | severe developmental delay, epilepsy, choreoathetosis, neutropenia | MMACHC | c.344C>T (p.Ala115Val) | WNL | ND | 626 |
| 6 | prenatal | severe developmental delay, infantile spasms with hypsarrythmia, microcephaly, IUGR | MMACHC | c.344C>T (p.Ala115Val) | ND | 22.7 | 192 |
| 7 | 4 months | epilepsy, hypotonia | MMACHC | c.344C>T (p.Ala115Val) | 118 | 11.6 | ND |
| 8 | <3 months | severe developmental delay, intractable epilepsy, hypospadias | MMACHC | c.344C>T (p.Ala115Val) | 80 | ND | elevated |
| 9 | <3 months | severe developmental delay, epilepsy, no eye contact, muscular hypotonia, microcephaly | MMACHC | c.344C>T (p.Ala115Val) | 61 | 5.5 | ND |
| 10 | 2 weeks | acute neurologic and metabolic decompensation, ketoacidosis with hyperammonemia, microcephaly, abnormal EEG, death in infancy | MMACHC | c.343G>A (p.Ala115Thr) | ND | elevated | elevated |
| 11 | 5 months | severe developmental delay, intractable epilepsy, choreoathetosis, FTT, ballismus | MMADHC, MMACHC | c.218C>Te (p.Ala73Val) | 9 | 5.7 | 127 |
| 12 | 9 weeks | severe developmental delay, epilepsy, muscular hypotonia, generalized disturbance and delay of myelination on MRI at age 8 years | MMACHC | c.218C>T (p.Ala73Val) | 13 | ND | 329 |
| 13 | 5 weeks | severe developmental delay, epilepsy, FTT | MMACHC | c.217G>A (p.Ala73Thr) | WNL | ND | elevated |
| 14 | prenatal | seizures, blindness, hearing impairment, slight dysmorphia, congenital microcephaly, IUGR, FTT | MMACHC | c.202C>G (p.Gln68Glu) | 87 | 23.0 | elevated |
Abbreviations are as follows: FTT, failure to thrive; IUGR, intrauterine growth retardation; ND, not determined; and WNL, within normal limits.
a
Normal is <13 μmol/l.
b
Normal is <0.4 μmol/l.
c
Normal is undetectable.
d
Mother was found to carry a de novo variant.
e
De novo variant.