Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5'-phosphate availability.
We describe two neonates presenting with perinatal hypophosphatasia and severe epileptic encephalopathy resulting in death. Both had increased levels of urinary vanillactate, indicating functional deficiency of aromatic amino acid decarboxylase, a pyridoxal-5-phosphate (PLP)-dependent enzyme required for dopamine and serotonin biosynthesis. Clinical findings and results of subsequent metabolic investigations were consistent with secondary pyridoxine-deficient encephalopathy. These patients highlight the importance of tissue non-specific alkaline phosphatase in the neuronal PLP-dependent metabolism of neurotransmitters. In addition, the disturbance of PLP metabolism appears to underlie the predominant neurological presentation in our patients. We recommend the measurement of serum alkaline phosphatase (ALP) during the assessment of perinatal seizures.
Balasubramaniam
Shanti
S
Genetic Metabolic Disorders Service, The Children's Hospital at Westmead, Sydney, Australia.
Bowling
Frank
F
Carpenter
Kevin
K
Earl
John
J
Chaitow
Jeffrey
J
Pitt
James
J
Mornet
Etienne
E
Sillence
David
D
Ellaway
Carolyn
C
D000469:Alkaline Phosphatase / Q000235:genetics* / Q000378:metabolism; D000927:Anticonvulsants / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007014:Hypophosphatasia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D011732:Pyridoxal Phosphate / Q000172:deficiency*; D011734:Pyridoxaminephosphate Oxidase / Q000172:deficiency* / Q000235:genetics; D012640:Seizures / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016896:Treatment Outcome; D026681:Vitamin B 6 Deficiency / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D014803:Vitamin B Complex / Q000627:therapeutic use
D000927:Anticonvulsants; D015306:Biogenic Monoamines; D014803:Vitamin B Complex; D011732:Pyridoxal Phosphate; D011734:Pyridoxaminephosphate Oxidase; C548267:ALPL protein, human; D000469:Alkaline Phosphatase