دراسة المظاهر السريرية و المورثية لحالات عوز الفينيل ألانين هيدروكسيلاز عند مرضى بيلة الفينيل كيتون في سورية

الملخص EN

Introduction: Phenylketonuria (PKU) manifests due to phenylalanine hydroxylase (PHA) deficiency.

PHA database provides information about the genetic basis of PHA and genotype-phenotype correlation.

This study describes the phenotype and genotype of 35 unrelated Syrians patients with phenylketonuria, and aims to show the rate of genotype-phenotype correlation and the predicting Biopterine responsiveness.

Methods: It is a prospective study of PKU diagnosed in patients followed by Metabolic diseases at Damascus University Children Hospital.

The genetic study was Conducded in the Atomic Research Center in Syria.

Patients were clinically classified using Gulberg classification.

Results: the study included 35 PKU patients mainly presented with psychomotor retardation (60%) at a mean age of 3 years, 65% presented classical PKU.

16 different mutations were found: missense 75.6%, splice site 33.4%, and frame shift 9%.

The predominant mutation was p.R261Q (12>6%) p.R243Q, p.F55>Lfs and IVS2+5G>C (8.75% for each).

Some rare variants were depicted.

Such as pS310F, Y387H, IVS9+G>A and p.D151G.

No data was shown for the last mutation.

Genotype-phenotype correlation was found positive in 40% of the cases and negative in 28.6% and unpredictable in 31%.

Biopterine responsiveness was estimated in 22.9%of the cases.

Conclusion: The diagnosis of the genetic type is very important and helpful in the management and prognostic prediction of PKU