Table 1

Clinical and biochemical findings in the patient cohort

							Physical appearance
Patient (sex)	Ancestry	Clinical Presentation	Gestational age and birth weight (centile)	Age at latest review	Height at review (centile)	Lactate	Short stature	Prominent forehead	Long/thin philtrum	Residual CI activity*	Identified by
1 (M)	English	RSV+ 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 <0.4th	9.5 years	<0.4th	+++	+	+	+	35%	Targeted NGS panel.
2 (F)	Irish	IUGR. Acute life-threatening event, age 20 days, required intubation. Hypertrophic cardiomyopathy.	30weeks 2nd	6 years	2nd	+	+	+	+	33%	Targeted NGS panel.
3 (F)	Irish	IUGR and oligohydramnios, FTT, mild hypertrophic cardiomyopathy.	34weeks 2nd–9th	3.5 years	0.4th–2nd	++	+	+	+	32%	Targeted NGS panel.
4 (F)	Irish	Growth 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 0.4th–2nd	8 years	n.d.	++	+	+	+	24%	Mutation screen.
5 (M)	Irish	IUGR. Poor feeding. Congenital hypothyroidism (strong paternal family history). Developmental delay, growth failure, FTT, learning difficulties. Endocrinology review for short stature.	37weeks 0.4th–2nd	10 years	0.4th	+	+	+	+	35%	Mutation screen.
6 (F)	Irish	Oligohydramnios. IUGR. Poor feeding at birth. MRI brain and echocardiogram normal. Age-appropriate skills. Family history of previous neonatal death.	37weeks <0.4th	2.5 years	2nd–9th	+++	+	+	+	35%	Mutation screen.
7 (M)	Irish	Sib of P6. IUGR. Normal echocardiogram and cranial ultrasound. Normal development.	36weeks 2nd–9th	10 months	9th	++	+	+	+	n.d.	Mutation screen.
8 (M)	Irish	Initial poor feeding. Short stature prompted endocrinology review. Growth hormone therapy. MRI: high signal in globus pallidus. Echo: murmur. ECG: Wolff–Parkinson–White syndrome.	Term 0.4th–2nd	9.5 years	2nd	−	+	+	+	n.d.	Whole-exome sequencing; endocrinology.
9 (F)	Irish	Sib of P8. IUGR. Growth hormone therapy. Normal MRI brain, echocardiogram and ECG.	Term <0.4th	8 years	2nd	−	+	+	+	n.d.	Whole-exome sequencing; endocrinology.
10 (M)	Irish	IUGR, 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 <0.4th	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.