Table 1

Clinical and biochemical findings in the patient cohort

Physical appearance
Patient (sex)AncestryClinical PresentationGestational age and birth weight (centile)Age at latest reviewHeight
at review (centile)
LactateShort statureProminent foreheadLong/thin philtrumResidual CI activity*Identified by
1 (M)EnglishRSV+ acute respiratory collapse and hypoglycaemia aged 8 weeks requiring intubation for 8 days. Pulmonary hypertension on echocardiogram. Maximum-recorded lactate 14 mmol/L. Discharged after 18 days. Normal cardiac function and morphology at 13 months.Term
9.5 years<0.4th++++++35%Targeted NGS panel.
2 (F)IrishIUGR. Acute life-threatening event, age 20 days, required intubation. Hypertrophic cardiomyopathy.30weeks
6 years2nd++++33%Targeted NGS panel.
3 (F)IrishIUGR and oligohydramnios, FTT, mild hypertrophic cardiomyopathy.34weeks
3.5 years0.4th–2nd+++++32%Targeted NGS panel.
4 (F)IrishGrowth restriction. Ketotic hypoglycaemia following vomiting illness. Short stature prompted endocrinology referral. Growth hormone therapy. MRI: high signal in periventricular white matter and dentate nuclei.39weeks
8 yearsn.d.+++++24%Mutation screen.
5 (M)IrishIUGR. Poor feeding. Congenital hypothyroidism (strong paternal family history). Developmental delay, growth failure, FTT, learning difficulties. Endocrinology review for short stature.37weeks
10 years0.4th++++35%Mutation screen.
6 (F)IrishOligohydramnios. IUGR. Poor feeding at birth. MRI brain and echocardiogram normal. Age-appropriate skills. Family history of previous neonatal death.37weeks
2.5 years2nd–9th++++++35%Mutation screen.
7 (M)IrishSib of P6. IUGR. Normal echocardiogram and cranial ultrasound. Normal development.36weeks
10 months9th+++++n.d.Mutation screen.
8 (M)IrishInitial poor feeding. Short stature prompted endocrinology review. Growth hormone therapy. MRI: high signal in globus pallidus. Echo: murmur. ECG: Wolff–Parkinson–White syndrome.Term
9.5 years2nd+++n.d.Whole-exome sequencing;
9 (F)IrishSib of P8. IUGR. Growth hormone therapy. Normal MRI brain, echocardiogram and ECG.Term
8 years2nd+++n.d.Whole-exome sequencing; endocrinology.
10 (M)IrishIUGR, chronic lung disease, growth restriction and weight faltering. Dysmorphic with partial agenesis of corpus callosum. Acute collapse with rhinovirus bronchiolitis, severe pulmonary hypertension at 5.5 months. Elevated lactates with intercurrent illnesses.31weeks
11 months<0.4th++++++36%Mutation screen.
  • *Residual Complex I activities, normalised to the activity of the matrix marker enzyme citrate synthase, are expressed as a percentage of mean control values. FTT, failure to thrive; IUGR, intrauterine growth restriction; N.D., not determined; NGS, next-generation sequencing; RSV, respiratory syncytial virus.