TABLE 1.
Characteristics and treatments of NADK2D cases
| Characteristic | Patient 1 | Patient 2 | Patient 3 | Our patient |
|---|---|---|---|---|
| Report | Roe et al. (1990) | Houten et al. (2014) | Tort et al. (2016) | |
| Gender | Female | Male | Female | Female |
| Onset | 2 days of age | 8 weeks of age | Birth | 9 years of age |
| Age/cause of death | 4 months: respiratory acidosis | 5 years | Alive at 10 years | Alive at 16 years |
| Developmental delay | Severe | Severe | Moderate | Normal |
| Neurological Findings | Severe encephalopathy, hypotonia, feeding difficulties & microcephaly | Severe encephalopathy, dystonia, cortical blindness, central apnea & intractable epilepsy | Axial hypotonia, uncoordinated movements, microcephaly, astatic myoclonic epilepsy | Optic atrophy, reduced vision, peripheral neuropathy & intermittent gait abnormalities |
| C10:2 carnitine | “Positive” on mass spectrometry | Positive (1.3umol/L | Positive (>0.11 umol/L) | Negative (<0.11 umoL/L) |
| Brain ultrasound/MRI | Bilateral ventriculomegaly | Progressive leukodystrophy, generalized cerebral atrophy, ventriculomegaly & bilateral basal ganglia T2 abnormalities | Ventriculomegaly, colpocephaly, and hypoplasia of the corpus callosum, generalized cerebellar atrophy | Age 9: Normal. Age 11: Optic pathway atrophy, parenchymal volume loss & abnormal morphology of the lateral ventricles with multiple septations within. |
| Plasma Lysine Levels | Elevated 5.0 times “upper limit of normal” 1052 nmol/L (normal 49–204 nmol/L) | Elevated 4.0 times “upper limit normal” 831 mol/L (normal 49–204 nmol/L) | “Elevated” (normal 49–204 nmol/L) | Elevated 3.7 times upper limit of normal- 890 nmol/L (103–255 mol/L) |
| Plasma proline levels | Normal (normal 85–303 nmol/L) | Normal (normal 85–303 nmol/L) | Normal (normal 85–303 nmol/L) | Elevated 2.5 times normal-920 nmol/L (normal 97–368 nmol/L) |
| NADK2 mutation | Not studied | Homozygous p.Arg340* c.1018C. T (NM_001085411.1) | Homozygous splice site (c.956 +6T>C; p.Trp319Cysfs*21) | Homozygous start loss g.36241900 T>C p. Met1Val |
| Therapy | Low-lysine formula (portagen®) & carnitine | Low-lysine diet, carnitine & medium chain fatty acid supplements | Low lysine diet, pyridoxal phosphate, biotin, thiamine, carnitine, creatine, vitamin E, idebenone & ubidecarenone supplements | NADH supplement |