Skip to main content

Table 3 Patients with confirmed inherited neurotransmitter disorders

From: Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study

Patients/sex/current age/diagnosis

Clinical features/age of onset/age of diagnosis

CSF* HVA/5-HIAA/ 3-OMD/THB/neo/other (LP age)

Molecular genetic testing reference

Treatment/outcome

1/M/9 yr/DHPR def

NBS-Pos-PKU/7 d/<15 d

↓123/↓55/↑2441/ ↓14 (3.5 yr) on treat

Homozygous novel IVS5+ 1 G > T in QDPR gene

L-dopa/carbidopa 9 mg/kg/d,5-HTP 7.5 mg/kg/d/severe GDD

2/F/3 yr/PTPS def

NBS-Pos-PKU/6 d/12 d

↓157/↓78/NP/↓ < 5/ ↑123 N (12 d)

Homozygous known [16] c.200C > T (p.Thr67Met) in PTS gene

L-dopa/carbidopa 7.13 mg/kg/d,5-HTP 2.59 mg/kg/d, sapropterin 2 mg/kg/d)/normal

3/F/14 yr/GTPCH def

GM delay, ataxia, tremor/17 mo/10 yr

↓121/N/N/↓8/↓ < 5 (13 yr)

Heterozygous known [17] c.225_225insA (pY75X) in GCH1 gene

L-dopa/carbidopa 8.5 mg/kg/d/executive dysfunction, intermittent dystonia, seizures

4/F/3 yr/TH def

GDD, choreoathetosis, dystonia/2 mo/24 mo

↓7/N/N (2 yr)

Homozygous known [18] c.943G > A (p.Gly315Ser) in TH gene

L-dopa/carbidopa 7.5 mg/kg/d/severe GDD, spasticity

5/F/5 yr/PDE-ALDH7A1

Seizures, GDD/3.5 mo/11 mo

↓175/↓110/N (7 mo)

Homozygous novel IVS-12(+1) G > A in ALDH7A1 gene

Pyridoxine 200 m/d/seizure free, severe GDD

6/F/1 yr/PNPO def

Neonatal MS, GTS/1 d/2 mo

N/N/↑329/↑threonine 107 (3 d)

Homozygous known [19] c.448_451del (p.Pro150Argfs*27) in PNPO gene

PLP 35 mg/k/d/seizure free, normal development

  1. Abbreviations: CSF cerebral spinal fluids, HVA homovanillic acid, 5-HIAA 5-hydroxyindol acetic acid, 3-OMD 3-O-methyldopa, LP lumbar puncture, THB tetrahydrobiopterin, Neo neopterin, DHPR dihydropterine reductase, def deficiency, GA-I glutaric aciduria type I, NBS-Pos-PKU newborn screening positive for phenylketonuria, d day(s), mo month(s), GDD global developmental delay, NP not performed, ProReD protein restricted diet, 5-HTP 5-hydroxytryptophane, PKU phenylketonuria, PTPS 6-pyruvoyl-tetrahydropterin synthase, GTPCH guanosine triphosphate cyclohydrolase, GM gross motor, TH tyrosine hydroxylase, PDE- ALDH7A1 pyridoxine dependent epilepsy caused by mutations in the ALDH7A1 gene, PNPO pyridox(am)ine-5-phosphate oxidase, MS myoclonic seizures, GTS generalized tonic seizures, PLP pyridoxal-5-phosphate, yr year(s), GTCS generalized tonic-clonic seizures. 3: ; ↑ = elevated; ↓ = decreased.
  2. *Age appropriate reference ranges for CSF neurotransmitters and amino acids: CSF HVA: 0–0.2 years = 337–1299 nmol/L; 0.2 - 0.5 years = 450–1132 nmol/L; 0.5 – 2 years = 294 – 1115 nmol/L; 2 – 5 years = 233–928 nmol/L; 5 – 10 years = 218–852 nmol/L; 10 – 15 years = 167–563 nmol/L; adults = 145–324 nmol/L.
  3. CSF 5HIAA: 0–0.2 years = 208 – 1159 nmol/L; 0.2 - 0.5 years = 179 – 711 nmol/L; 0.5 - 2 years = 129 – 520 nmol/L; 2 – 5 years = 74 – 345 nmol/L; 5 – 10 years = 66 – 338 nmol/L; 10 – 15 years = 67 – 189; adults = 67–140 nmol/L.
  4. CSF 3-O-MD: 0–0.2 years = <300 nmol/L; 0.2 - 0.5 years = <300 nmol/L; 0.5 – 2 years = <300 nmol/L; 2 – 5 years = <150 nmol/L; 5 – 10 years = <100 nmol/L; 10 – 15 years = <100 nmol/L; adults = <100 nmol/L.
  5. CSF tetrahydrobiopterin: 0–0.2 years = 40–105 nmol/L; 0.2-0.5 years = 23–98 nmol/L; 0.5-2 years = 18–58 nmol/L; 5–10 years = 9–40 nmol/L; 10–15 years = 9–32 nmol/L; adults = 10–30 nmol/L.
  6. CSF neopterin: 0–0.2 years = 7–65 nmol/L; 0.2-0.5 years = 7–65 nmol/L; 0.5-2 years = 7–65 nmol/L; 2–5 years = 7–65 nmol/L; 5–10 years = 7–40 nmol/L; 10–15 years = 8–33 nmol/L; adults = 8–28 nmol/L.
  7. CSF threonine: 28–92 μmol/L.
Back to article page

Orphanet Journal of Rare Diseases

ISSN: 1750-1172