Table 3 Summary of clinical, biochemical and genetic features associated with ETFDH variants of neonatal GA II
Patient1 | Patient2 | Patient3 | |
|---|---|---|---|
Gender | Male | Male | Female |
Origin | Caucasian Afrikaner | Kurdish origin | Chinese |
Age of onset/death | Week 1/Day 9 | 3 months/ 34 months | Day 1/ Day 24 |
Main clinical features | Intra-uterine growth retardation Multiple congenital anomalies: • Cardiac lesions • Hydronephrosis Riboflavin unresponsive | Profound hypotonia and hepatomegaly. White matter signal abnormalities on brain MRI Riboflavin responsive | Poor sucking and response, fever, hypotonia, seizures Purulent meningitis and septicemia |
Routine Biochemistry | |||
• Metabolic acidosis | Present | Not performed | Present |
• Glucose | Normal-↓ | ↓-Normal | ↓ |
• Ammonia | ↑ | ↑ | ↑ |
• Urine ketones | Absent | Not performed | Not performed |
• Lactate/pyruvate | Normal-↑ | ↑ | ↑ |
Transaminases | ↑GGT, AST | ALT↑ | GGT, AST, ALP↑ |
Creatine kinase | Not performed | normal | Not performed |
CBC findings | Pancytopenia | Not performed | White blood cells and neutrophils↑ |
Metabolic findings | |||
Acylcarnitines | ↑C4-, C5, C5-DC Low free carnitine | ↑C8, C10, C12, C14 Normal free carnitine | ↑C4-, C5, C5-DC, C6, C8, C10, C12, C14, C16, C18 |
Organic acids | ↑Ethylmalonic acid, Dicarboxylic acids, Glycine conjugates, 2-Hydroxryglutaric acid Lactic acid, Krebs cycle intermediates | ↑Glutaric acid, Dicarboxylic aciduria 2-Hydroxyglutaric acid | ↑Glutaric acid, OX-2-Acetoacetic acid, 2-Hydroxy isobutyric acid-2, adipic acid, isovalanyl glycine-2, |
Amino acids | General amino aciduria with ↑ Sarcosine | ↑Threonine, serine, asparagine, glycine, alanine, β-aminoisobutyric acid, and lysine. | ↑Citrulline |
ETFDH variants | c.1067G > A/ c.1067G > A | c.1141G > C/ c.1141G > C | c.1399 G > C/ c.623_626 del |
Reference | F.H. van der Westhuizen et al. [11] | Vieira et al. [12] | Our study |