Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder

Table 2 Correlates of clinical severity with age, and age-adjusted biochemical, neurophysiologic, and neuroimaging biomarkers

Characteristic	Total CSS	Cognitive Domain	Communication Domain	Motor Domain	Epilepsy Domain	Psychiatric Domain
	R	R	R	R	R	R
	p value	p value	p value	p value	p value	p value
Age	-0.302	-0.054	0.31	0.368	-0.576	-0.522
Age	0.03	0.71	0.03	0.009	< 0.001	< 0.001
Gene expression, 2^ΔCT
ALDH5A1 (N = 23)	0.154	0.038	-0.173	0.179	-0.113	0.418
	0.49	0.86	0.44	0.42	0.62	0.05
ABAT (N = 23)	-0.232	-0.568	0.272	0.156	-0.3	-0.089
	0.29	0.006	0.22	0.48	0.17	0.69
GLS (N = 23)	-0.008	-0.299	0.245	0.195	0.054	-0.1
	0.97	0.17	0.27	0.38	0.81	0.65
GLUL (N = 23)	-0.092	-0.104	-0.131	-0.325	-0.072	0.163
	0.68	0.64	0.56	0.14	0.75	0.68
GLUD1 (N = 23)	-0.064	-0.367	0.151	0.196	0.073	-0.137
	0.77	0.09	0.5	0.38	0.74	0.54
Biochemical
Plasma GABA, µM/L (N = 43)	0.337	0.067	0.149	-0.149	0.402	0.354
	0.02	0.66	0.33	0.33	0.007	0.01
Plasma GHB, µM/L (N = 35)	0.36	0.145	0.18	-0.11	0.215	0.431
	0.05	0.44	0.34	0.95	0.25	0.01
MRS
GABA/NAA, (BG, PCG, OCC)* (N = 16)	0.031	-0.225	0.201	-0.231	0.211	0.24
	0.9	0.37	0.42	0.35	0.4	0.33
TMS
rMT, %MO (N = 23)	-0.312	-0.19	-0.262	-0.215	-0.095	-0.227
	0.15	0.39	0.23	0.33	0.67	0.31
CSP, ms (N = 21)	-0.085	-0.281	0.054	0.36	0.045	-0.234
	0.72	0.23	0.82	0.11	0.85	0.32
LICI, log (MEPt/MEPc) (N = 18)	-0.264	-0.295	-0.031	-0.211	-0.101	-0.123
	0.3	0.25	0.9	0.416	0.7	0.63

ABAT- 4-aminobutyrate aminotransferase; ADOS-2- Autism Diagnostic Observation Schedule-Second Edition; ALDH5A1- Aldehyde dehydrogenase 5 family member A1; ASD- Autism Spectrum Disorder; BG- basal ganglia; CSP- cortical silent period; EEG- Electroencephalogram; EEM- estimated marginal means adjusted for age; FSIQ- full-scale intellectual quotient; GABA- γ-aminobutyrate; GHB- γ-hydroxybutyrate; GLS- Glutaminase; GLUD1- Glutamate dehydrogenase 1; GLUL- Glutamate-ammonia ligase; IQR- Interquartile ratio; LICI- long interval intracortical inhibition; MEPc- motor evoked potential, condition; MEPt- motor evoked potential, test; MO- machine output; MRS- Magnetic resonance spectroscopy; ms- milliseconds; NAA- N-acetyl aspartate; OCC- occipital cortex; PCG- posterior cingulate gyrus; R- correlation coefficient; SD- Standard deviation; SE- standard error; SSADHD- succinic semialdehyde dehydrogenase deficiency; TMS- transcranial magnetic stimulation; Bold indicates significant. *Mean value of the GABA/NAA ratios measured from the basal ganglia, posterior cingulate gyrus, and occipital cortex)

ISSN: 1866-1955