Table 2.

Treatable Disorders Associated with Early Infantile-Onset Epileptic Encephalopathy

ConditionsGene(s)MOIClinical FindingsTreatment
Neuro-
metabolic
disorders 		Pyridoxine-dependent epilepsy ALDH7A1 AR
  • ↑ plasma & urine alpha-aminoadipic semialdehyde
  • ↑ plasma & CSF pipecolic acid
Seizures/encephalopathy responsive to pyridoxine
Pyridoxamine 5'-phosphate oxidase deficiency (OMIM 610090) PNPO AR
  • Lactic acidemia
  • Hypoglycemia
Seizures/encephalopathy responsive to pyridoxal 5-prime phosphate
Biotinidase deficiency BTD AR
  • Deficient biotinidase enzyme activity in serum or plasma
  • Ketolactic acidosis, organic aciduria, hyperammonemia
  • Skin rash, alopecia, recurrent viral or fungal infections
Lifelong biotin supplementation
Glucose transporter 1 deficiency syndrome SLC2A1 AD
AR
  • ↓ CSF glucose concentration
  • Absence seizures beginning age <3
Ketogenic diet

Creatine deficiency syndromes

GAMT
GATM
SCL6A8 		AR
XL
  • Cerebral creatine deficiency on brain MR spectroscopy
  • Suggestive ratio of guanidinoacetate, creatine, &/or creatinine in plasma & urine
Creatine monohydrate supplementation
Holocarboxylase synthetase deficiency (OMIM 253270) HLCS AR
  • Ketolactic acidosis, organic aciduria, hyperammonemia
  • Skin rash, alopecia
Responsive to biotin
Serine biosynthesis disorders PHGDH
PSAT1
PSPH 		AR
  • Congenital or acquired microcephaly, congenital cataracts
  • ↓ plasma & CSF serine
L-serine & glycine supplementation can reduce seizures, improve psychomotor symptoms, & prevent progression depending on subtype
Other Infection of the CNSNAMRI, blood culture &/or lumbar puncture suggestive of infectionAntibiotic, antiviral, or antifungal therapy
Structural brain lesionsNA(Multi)focal lesions on brain MRI

Tuberous sclerosis complex

TSC1
TCS2
  • MRI brain lesions (subependymal nodules, subependymal giant cell astrocytomas, tubers, focal cortical dysplasias)
  • Cardiac rhabdomyoma, skin lesions, retinal lesions, renal lesions
Consideration of mTOR inhibitor for astrocytoma, additional seizure reduction
ARX-associated encephalopathy (OMIM 308350) ARX Enlarged ventricles & T2-weighted signals in basal ganglia on brain MRI

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; NA = not applicable; XL = X-linked

From: KCNT1-Related Epilepsy

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