Table 1. Clinical and laboratory profiles of study populations.
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | |
|---|---|---|---|---|---|---|
| Age at first visit (mo) | 83 | 16 | 14 | 26 | 16 | 58 |
| Sex | F | F | M | M | M | M |
| GDD/regression | + | + | + | + | + | + |
| Family history | + | + | + | + | − | − |
| Consanguinity | + | + | + | + | + | + |
| Petechiae/purpura | + | + | + | + | + | + |
| Chronic diarrhea | + | + | + | + | + | − |
| Recurrent encephalopathy | + | − | + | − | + | + |
| Acrocyanosis | − | − | − | − | + | + |
| Weight (kg) | 18 | 8 | 6.5 | 8 | 7 | 12 |
| WHO z-score for weight | 25–50th P a | 0 to −2 z | < − 3 z | < − 3 z | < − 3 z | −3 z |
| Length (cm) | 112 | 68 | 67 | 73 | 68 | 101 |
| WHO z-score for length | 10–25th P a | < − 3 z | < − 3 z | < − 3 z | < − 3 | 0 to −2 z |
| Head circumference (cm) | 46 | 42 | 42 | 43 | 42 | 43 |
| WHO z-score for head | < − 3 z | < − 3 z | < − 3 z | < − 3 z | < − 3 z | < − 3 z |
| Hypotonia | + | + | − | + | + | + |
| Hypertonia | − | − | + | − | − | − |
| Exaggerated DTR | + | + | + | + | + | + |
| Dystonia | + | − | + | − | + | − |
| Seizures | − | + | − | − | + | + |
| Feeding difficulty | + | − | + | + | + | + |
| ABG anion gap acidosis (normal: 8–16 mEq/L) | 22 | 15 | 13 | 23 | 13 | 12 |
| Arterial lactate (normal: 10–20 mg/dL) | 45 | 50 | 16 | 46 | 53 | 17 |
| Serum butyrylcarnitine C4 (normal: 0–1.30 µmol/L) | 1.4 | 1.5 | 1.35 | 1.6 | 1.35 | 1.6 |
| Urinary EMA (normal: <8.5 mmol/mol creatinine) | 45 | 35 | 45 | ND | 23 | 44 |
| MRI brain: patchy T2 hyperintensities | ||||||
| Caudate and putamen | + | + | + | + | + | + |
| Thalamus | + | + | + | + | + | + |
| Dorsal pons and dental nuclei | − | − | − | − | − | + |
| Pathogenic variant in ETHE1 gene |
ND | ND | ND | ND | Exon-5 c.548T > C p. Phe183Ser | Exon 4. c.487C > G P. Arg163Gly |
| Metronidazole 20 mg/kg/day twice daily on alternate week | − | + | − | + | + | + |
| Diet: low methionine and cysteine | + | + | + | + | + | + |
| NAC 100 mg/kg/day twice daily | − | + | − | + | + | + |
| Outcome | Died | Died | Died | Died | GDD/FTT | GDD/FTT |
Abbreviations: ABG, arterial blood gas; DTR, deep tendon reflexes; EMA, ethylmalonic acid; F, female; FTT, failure to thrive; GDD, global developmental delay; M, male; MRI, magnetic resonance imaging; NAC, N -acetylcysteine; ND, not done; P, percentile; +, yes; −, no.
a
For case 1, weight and length are in percentile as per the Indian Academy of Pediatrics standards and for the others cases they are in WHO z-score.