TY - JOUR
T1 - Pyridoxal phosphate-responsive seizures in a patient with cerebral folate deficiency (CFD) and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM)
AU - Dill, Patricia
AU - Schneider, Jacques
AU - Weber, Peter
AU - Trachsel, Daniel
AU - Tekin, Mustafa
AU - Jakobs, Cornelis
AU - Thöny, Beat
AU - Blau, Nenad
N1 - Funding Information:
First of all the authors would like to thank the parents for the generous permission to publish detailed information about their son. In addition the authors would like to thank David Meili, Anahita Rassi, and Asli Sirmaci for the excellent technical help. This work was supported in part by The Swiss National Science Foundation grant no. 3100A0-1199852/1 (to NB and BT).
PY - 2011/11
Y1 - 2011/11
N2 - We present an 8-year-old boy with folate receptor alpha (FRα) defect and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM syndrome). Both conditions are exceptionally rare autosomal recessive inherited diseases mapped to 11q13. Our patient was found to have novel homozygous nonsense mutations in the FOLR1 gene (p.R204X), and FGF3 gene (p.C50X). While the FRα defect is a disorder of brain-specific folate transport accompanied with cerebral folate deficiency (CFD) causing progressive neurological symptoms, LAMM syndrome is a solely malformative condition, with normal physical growth and cognitive development. Our patient presented with congenital deafness, hypotonia, dysphygia and ataxia in early childhood. At the age of 6. years he developed intractable epilepsy, and deteriorated clinically with respiratory arrest and severe hypercapnea at the age of 8. years. In contrast to the previously published patients with a FOLR1 gene defect, our patient presented with an abnormal l-dopa metabolism in CSF and high 3-O-methyl-dopa. Upon oral treatment with folinic acid the boy regained consciousness while the epilepsy could be successfully managed only with additional pyridoxal 5'-phosphate (PLP).This report pinpoints the importance of CSF folate investigations in children with unexplained progressive neurological presentations, even if a malformative syndrome is obviously present, and suggests a trial with PLP in folinic acid-unresponsive seizures.
AB - We present an 8-year-old boy with folate receptor alpha (FRα) defect and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM syndrome). Both conditions are exceptionally rare autosomal recessive inherited diseases mapped to 11q13. Our patient was found to have novel homozygous nonsense mutations in the FOLR1 gene (p.R204X), and FGF3 gene (p.C50X). While the FRα defect is a disorder of brain-specific folate transport accompanied with cerebral folate deficiency (CFD) causing progressive neurological symptoms, LAMM syndrome is a solely malformative condition, with normal physical growth and cognitive development. Our patient presented with congenital deafness, hypotonia, dysphygia and ataxia in early childhood. At the age of 6. years he developed intractable epilepsy, and deteriorated clinically with respiratory arrest and severe hypercapnea at the age of 8. years. In contrast to the previously published patients with a FOLR1 gene defect, our patient presented with an abnormal l-dopa metabolism in CSF and high 3-O-methyl-dopa. Upon oral treatment with folinic acid the boy regained consciousness while the epilepsy could be successfully managed only with additional pyridoxal 5'-phosphate (PLP).This report pinpoints the importance of CSF folate investigations in children with unexplained progressive neurological presentations, even if a malformative syndrome is obviously present, and suggests a trial with PLP in folinic acid-unresponsive seizures.
KW - Cerebral folate deficiency
KW - Epilepsy
KW - FGF3 gene
KW - FOLR1 gene
KW - Labyrinthine aplasia
KW - Leucodystrophy
UR - http://www.scopus.com/inward/record.url?scp=82455171659&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82455171659&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2011.05.019
DO - 10.1016/j.ymgme.2011.05.019
M3 - Article
C2 - 21752681
AN - SCOPUS:82455171659
VL - 104
SP - 362
EP - 368
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 3
ER -