الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Phenylketonuria is one of the preventable inherited causes of intellectual disability. The major cause is deficiency of the hepatic enzyme phenylalanine hydroxylase, which is responsible for conversion of phenylalanine (Phe) into tyrosine (Tyr) due to biallelic mutations in the coding gene of PAH. Early diagnosis and management is the key for avoidance of its complications, which include irreversible intellectual disability, microcephaly, developmental delay, motor deficits, seizures and autism. The corner stone of the management is the dietary regimen, which depends on two main items namely the low- Phe diet and the Phe free amino acid formula. Future prospective includes clinical trials on enzyme replacement therapy using modified phenylalanine ammonia lyase enzyme. Phase II clinical trials showed encouraging results. On the other hand, various studies investigated the effectiveness of gene therapy including the use of vectors containing genes coding for PAH enzyme and its cofactor BH4 into the muscular tissue of PKU mouse model with successful conversion of Phe into Tyr. These future therapies may have the potential to enable PKU patients to free their dietary restriction and lead normal life.
The current study was conducted on 104 phenylketonuria (PKU) children for clinical, biochemical and molecular characterization. Patients were assessed clinically and neurologically. Recording of anthropometric measurements, parental consanguinity, level of parental education, age at diagnosis and developmental history was done. Compliance to the dietary therapy in addition to monthly blood Phe measurements for three consecutive months were followed- up. Cases were selected for full PAH gene bidirectional Sanger dideoxy chain termination sequencing as a pilot study for genotype- phenotype correlation from patients with high Phe tolerance and from patients with low Phe tolerance.
The overall age range was 1.0 to 17.50. About 51% were males and 49% were females. The male to female ratio was 1.03: 1 which is consistent with the disease pattern of inheritance being autosomal recessive.
Patients were categorized according to the age at diagnosis into three groups. About 76% were early diagnosed before the age of three months, whereas 21.1 % of the patients were diagnosed at the age of three months up to less than seven years (i.e. late diagnoed). Nearly 2.9% of the patients were diagnosed at the age of seven years or more (i.e. untreated).
Regarding weight, 3.8% of group (1) and 4.5% of group (2) were underweight. Overweight was encountered in 10.1% of group (1) and 13.6% of group (2), while obesity was detected in 5.1% of group (1) and 13.6% of group (2). As for height, 12.7% of group (1) and 9.1% of group (2) had short stature. group (3) patients had normal weight and height. Neither of the patients in the three groups was microcephalic (i.e. > 3SD below normal for age).
Delayed fine- motor development was detected in 5.1% of group (1) patients compared to 81.1% of group (2) and 100% of group (3). The difference between the three groups is statistically significant. Regarding gross- motor developmental delay, it was detected in 27.3% of group (2) and 66.7% of group (3) compared to 1.3% in group (1). The difference between the three groups is statistically significant.