Table 3.

Clinical investigations (MRI, EEG and metabolic laboratory tests) of subjects with biallelic variants in SLC38A3

	Family 1		Family 2	Family 3	Family 4	Family 5	Family 6			Family 7
	II-2	II-3	II-3	II-4a	II-1	II-3	II-3	II-4	III-1	II-5
Neurophysiological studies (EEG)
Diffuse background slowing	+	+	+	+	−	+	−	N/A	−	+	6/10
Epileptiform activity	+	+	+	+	−	−	−	+	−	+	6/10
LTM-EEG	Frequent tonic seizures with eyelid myoclonia over 48 h	20 GTC and 4 focal seizures over 24 h	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Frequent generalized myoclonic and tonic seizures over 48 h
Brain imaging
Study type	Brain MRI	Brain MRI	Brain MRI	Brain MRI	Brain MRI	Brain MRI	Head CT	Head CT	Brain MRI	Brain MRI
Cerebral atrophy	+	+	−	+	−	+	−	−	+	−	5/10
Cerebellar atrophy	+	+	−	−	−	−	−	−	−	−	2/10
CC abnormality	+	+	+	+	−	+	−	−	+	−	6/10
Under-opercularization	+	+	−	+	−	−	−	+	+	+	6/10
Abnormal myelination	+	+	−	+	−	+	−	−	+	+	6/10
Others	Thin brainstem					Generous extra-axial CSF spaces	–	Dolichocephaly, mild posterior plagiocephaly	Generous extra-axial CSF spaces; mild superior vermian hypoplasia	Generous extra-axial CSF spaces
Brain MRS findings	Low NAA and Glx peaks	Lactate peak	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Metabolic laboratory studies
Plasma lactate and pyruvate	Normal	Transient elevation of lactate	Transient metabolic acidosis (due to TPM use)	Transient elevation of lactate and pyruvate	Transient elevation of lactate and pyruvate	Normal	Slightly elevated lactate	Transient elevation of lactate; normal pyruvate	Elevated lactate	Transient elevation of lactate
Plasma ammonia	Normal	Elevated (62 µmol/l)	N/A	N/A	Normal (25 µmol/l)	N/A	Elevated (52 µmol/l)	Elevated (56 µmol/l)	Elevated (87 µmol/l)	Normal (44 µmol/l)
PAA	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal
UOA	Normal	Normal	Normal	N/A	Normal	Normal	Normal	Normal	Normal	Normal
CSF amino acids	Normal	Normal	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
CSF neurotransmitters	Normal	Normal	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
CSF lactate	N/A	Normal	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A

CC = corpus callosum; c/w = consistent with; Glx = glutamate-glutamine; GTC = generalized tonic-clonic; LTM-EEG = long-term monitoring EEG; MRS = magnetic resonance spectroscopy; NAA = N-acetylaspartate; N/A = not available; PAA = plasma amino acids; TPM = topiramate; UOA = urine organic acids.

^aPreviously published with limited clinical data.