Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway.
We present the first two identified cases of phosphoserine aminotransferase deficiency. This disorder of serine biosynthesis has been identified in two siblings who showed low concentrations of serine and glycine in plasma and cerebrospinal fluid. Clinically, the index patient presented with intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation and died at age 7 mo despite supplementation with serine (500 mg/kg/d) and glycine (200 mg/kg/d) from age 11 wk. The younger sibling received treatment from birth, which led to a normal outcome at age 3 years. Measurement of phosphoserine aminotransferase activity in cultured fibroblasts in the index patient was inconclusive, but mutational analysis revealed compound heterozygosity for two mutations in the PSAT1 gene--one frameshift mutation (c.delG107) and one missense mutation (c.299A-->C [p.Asp100Ala])--in both siblings. Expression studies of the p.Asp100Ala mutant protein revealed a V(max) of only 15% of that of the wild-type protein.
Hart
Claire E
CE
Departments of Clinical Chemistry, Sheffield Children's Hospital, Sheffield, UK.
Race
Valerie
V
Achouri
Younes
Y
Wiame
Elsa
E
Sharrard
Mark
M
Olpin
Simon E
SE
Watkinson
Jennifer
J
Bonham
James R
JR
Jaeken
Jaak
J
Matthijs
Gert
G
Van Schaftingen
Emile
E
D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005998:Glycine / Q000172:deficiency / Q000627:therapeutic use; D006579:Heterozygote; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000096:biosynthesis* / Q000172:deficiency / Q000627:therapeutic use; D000637:Transaminases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
D011994:Recombinant Proteins; D012694:Serine; D004247:DNA; D000637:Transaminases; C022393:phosphoserine aminotransferase; D005998:Glycine