Case#: Case report, 8 year old (report), male
CaseHPOs: See free text
CaseHPOsFreeText: In the newborn period – hypotonia, torticollis, right inguinal hernia (surgically repaired). Concern about delays at 4 months of age. First evaluated at 19 months. No NAA or NAAG signal on neurospectroscopy (at 2 years 3 months, and 3 years 6 months). At 8 years, “profound neurological dysfunction”, can walk unaided for short distances, ataxic gait, no speech but can make sounds, behavior abnormalities, microcephaly, profound intellectual impairment (<12 month level), generalized seizures beginning at 5 year 9 months of age with 9 episodes of status epilepticus, tendency to self mutilation if left alone, drools.
CaseNotHPOs: No dysmorphic features. Normal vision and hearing. Normal brain anatomy on MRI.
CasePreviousTesting: MR spectra of urine, plasma, and CSF were unremarkable (3 years 10 months, 5 years 6 months). The latter samples were analyzed by capillary electrophoresis (CE) and revealed no detectable NAA in CSF (this is also seen in controls, and therefore normal). No detectable NAAG (usually in the uM range in controls). CE of urine – NAA 21.0 umol/mmol creatinine and NAAG 1.9 umol/mmol creatinine (within the normal range). Normal plasma amino acids, urine organic acids, oligosaccharides, mucopolysaccharides. No evidence for mitochondrial, organic acid, amino acid, or peroxisomal disorder. CSF normal for cell count, glucose, protein, biogenic amines, folates, and pterins (on two occasions).
CaseMethod1: PCR
CaseMethod2: Sequencing
CaseGenotypingMethod: The three exons of NAT8L were amplified and sequenced.
Variant: NM_178557.4(NAT8L):c.212_230del (p.Gly71fs)
ClinVar: 30849
gnomAD: Not in gnomAD
VariantEvidence: Expression of cDNA containing the variant in HEK-293 cells resulted in no enzyme activity and no cross-reactive material.
CaseAddInfo: “Born in an Eastern European country”, adopted by a family is Switzerland. Exposure to cigarettes and alcohol during the pregnancy.
CasePMIDs: 15328569, 16802720