[Clinical, biomedical , neurological and molecular study of 11 patients with new mutations in PAH gene].
BACKGROUND
PKU is an autosomal recessive disorder. There is a broad spectrum phenotype which depends mainly on residual enzymatic activity and also on other factors such as modifying genes and non-genetic factors. This fact makes us consider that a multidisciplinary study of these patients is necessary to improve knowledge of the condition.


OBJECTIVE
To establish phenotype-genotype correlation and classify nine new mutations according to severity.


METHODS
We evaluated the clinical data obtained from a multidisciplinary trial of 11 patients with PKU/HPA who presented with nine new mutations (P275S, P279fsdelC, V388delTG, N61/I62/T63fsdel5bp, P281S, P362T, H1OOR, I164V and Y168H) identified during a molecular study of the PAH gene done in Catalonia (Spain).


CONCLUSIONS
In our patients the genotype is correlated with the biochemical phenotype whereas the cognitive phenotype depends on determining factors such as early diagnosis and diet. Therefore, although PKU may be considered to be a complex characteristic, the mutations in the PAH gene are the main determining factor of the metabolic phenotype of PKU. A multidisciplinary study is the best way to understand and control these patients.
Mallolas
J
J
Servicio de Genética, Hospital Clínic, Hospital Sant Joan de Déu, Barcelona, España. mmila@clinic.ub.es
Vilaseca
M A
MA
Campistol
J
J
Lambruschini
N
N
Cambra
F J
FJ
Fusté
M E
ME
Milà
M
M
D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009483:Neuropsychological Tests; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000097:blood / Q000235:genetics*; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012720:Severity of Illness Index
D010651:Phenylalanine Hydroxylase