Table 2.

Genotype and phenotypic features observed in 5 patients described so far with FOXRED1 deficiency.

Case #	Genetic mutation	Zygosity	Clinical diagnosis	Metabolic/biochemical findings	Neurological findings	MRI features
Case 1 [2]	p.R352W/(p.Arg352Trp) c.1054C > T missense variant	Homozygous	Leigh syndrome	Elevated plasma lactate	Severe truncal hypotonia/Mitochondrial encephalopathy	Delayed myelination, ventricular dilatation and abnormal signal in thalami and basal ganglia
				Decreased level of C I
Case 2 [1]	p.N430S/(p.Asn430Ser) c.1289A > G missense variant	Compound heterozygous	Leigh syndrome	Hypoglycemia Lactic acidosis Decreased level of C I	Hypotonia Athetoid movements	Decreased attenuation in the putamen bilaterally and significant cerebellar atrophy
	p.Q232X/(p.Gln232Ter) c.694C > T nonsense variant
Case 3 [3]	p.V421 M/(p.Val421Met) c.1308G > A missense variant	Homozygous	Severe encephalopathy	Complex I and II deficiency	Epilepsy Severe psychomotor retardation	Delayed myelination, ventricular dilatation and abnormal signal in the thalami and basal ganglia
Case 4 [5]	c.406C > T; p.R136W missense variant c.612_615dupAGTG; p.Ala206SerfsX15 frameshift variant	Compound heterozygous	(Clinical diagnosis not defined)	Complex I activity <25	N/A	N/A
Case 5 (our index case)	c.612_615dupAGTG	Compound heterozygous	Neonatal lactic acidosis, cerebral cysts and Pulmonary Hypertension	Decreased activity of complex I (Decreased C I and II)	Mild hypertonia, wrist and ankle contracture. Seizures.	Diffusely abnormal brain with large periventricular cysts, edematous white matter, delayed myelination, thin and undersulcated cortex particularly anteriorly
	p. Ala206SfsX15 frameshift variant
	p.G292R/(p. Gly292Arg) c.874G > A missense variant