الفهرس 
Qinical Manifestations of PhenylketonuriaOnly 14 pages are availabe for public view
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Abstract
Phenylketonuria (PKU) is a rare genetic disorder that results in excessive accumulation of the
amino acid PHE and reduced levels of the amino acid L-tyrosine in the blood. If untreated, high
levels of PHE can cause severe mental retardation, behavioral disturbances, and other neurological
problems. Through routine newborn screening, almost all affected newborns could be diagnosed and
treated early, allowing them to grow up free of mental retardation and other PKU related
conditions.
Because nationwide neonatal screening program for PKU was not available in Egypt till the time of
conduction of the current study, it was carried out to assess the psychiatric, behavioral and
neurological disorders in a sample of Egyptian patients with PKU. Also, the present study
investigated the psychosocial impact of such an illness with its peculiarity on caregivers. An
Intervention Program aiming at education of caregivers about the disease was implemented with
evaluation of its role in improving disease knowledge of the enrolled caregivers.
A prospective study with an intervention domain was carried out on a random sample of Egyptian
patients with PKU chosen from the Genetics Clinic, Children’s Hospital, Ain Shams
University. They were 20 cases; II and 9 r3 aged from 2.5 to 15
yrs with a mean age of 7.3 ± 3.87 yrs and a median of 6.33 yrs.
Household caregivers of studied cases were also enrolled after taking their consent.
Full history taking, family pedigree construction, thorough clinical examination, plasma PHE level
assessment, EEG recording, IQ assessment, PCL scoring with assessment of
behavior problems, and psychiatric disorders diagnosis using DSM IV criteria were done for all
studied patients. On the other hand, preliminary interview, assessment of SES, FSF score, DAI
score, and a specially designed DKQ score before and after the implementation of the used IP were
carried out for all enrolled caregivers. Confirmation of clinically manifest psychiatric disorders
in caregivers was done using DSM IV criteria.
The overall consanguinity rate recorded in the present study was 75% with a prevalence of family
history of PKU of 55%. The most prevalent SE levels among enrolled families were the Low (40%) and
the very low (25%).
All studied cases had behavior and or psychiatric disorders. These disorders included anxiety
disorders (70%), ADHD (60%), depression (55%), vegetative disorders (30%), conduct disorders (15%),
POD (10%), and psychotic disorder (5%).
Mental retardation with different degrees was recorded in 85% of enrolled cases while pyramidal,
and extra-pyramidal signs were clinically detected in 25% and 10% respectively. Generalized
tonic-clonic fits were reported in 20% while EEG changes were detected in 35% of the studied
sample.
Average plasma PHE level ranged from 6 to 22 mg/dl with a mean value of 14.78 ± 5.54 mg/dl while
PCL score ranged between 18 and 38 with a mean value of27.85± 4.65.
DKQ score showed significant improvement after the implementation of IP when compared with DKQ
score before the use of that IP; p 0.001. Maternal caregivers had significantly higher AS, OS, and
IS when compared to paternal caregivers; p
0.001 in all. Also, the prevalence of clinically manifest anxiety, depression, and isolation were
significantly higher in maternal caregivers compared to paternal caregivers, p 0.05, p 0.01, p
0.001 respectively.
Maintaining dietary restriction of PHE was considered difficult by all caregivers of enrolled
patients because of different reasons. These reasons included: rarely available low PHE formulas
and foods (I00%), the high cost of such formulas and foods (90%) and their bad taste (60%).
Other problems faced studied caregivers in raising their affected
children were dealing with their behavior problems (100%), expenses of the follow up assessment of
plasma PHE level (90%), guilt feeling because of eating foods their diseased children could not eat
(40%) as well as rarity and expenses of places offering proper rehabilitation programs (40%).
In the current study, patients who followed the dietary therapy regularly showed significantly
lower average plasma PHE level, higher IQ, lower PCL score (better psychosocial function), higher
mental age, and lesser mental age and language age delay. On the other hand, paternal isolation
score was significantly higher among paternal caregivers of cases with IDT.
Cases with PKU who were diagnosed and treated > 2 yrs showed significantly lower IQ, higher PCL
scores (poorer psychosocial function), and more mental age delay compared to those diagnosed 2
yrs. On the other hand, caregivers of enrolled cases diagnosed and treated > 2 yrs had
significantly higher mean value of paternal depression score as well as higher prevalence rates of
paternal depression and paternal isolation compared to caregivers of cases diagnosed and treated
2 yrs.
Using an Arabic-Pediatric Check list (PCL) showed that 65% of cases enrolled in the present study
had psychosocial dysfunction (PSD) because of their behavior problems (cut-off value of PCL scores
2: 28). Patients with PSD were significantly older compared to those with fair psychosocial
function (p ::; 0.05). On the other hand, cases enrolled in the present study that had PSD showed
significantly lower prevalence of RDT (p ::; 0.05) and thus higher mean average plasma PHE (p <
0.05) compared to those with fair psychosocial function. Meanwhile, cases with PSD had
significantly lower IQ and more MAD compared to those with fair psychosocial function (p ::; 0.05;
p < 0.05 respectively). Comparison between patients with PSD and those with fair psychosocial
function revealed statistically insignificant differences as regards LAD, FSF, family Socioeconomic
score (FSE score), Disease Knowledge Questionnaire (DKQ) scores before & after the implemented
Intervention Program (IP), maternal and paternal DAI scores; and the prevalence of different
socioeconomic levels, family PSD, and clinically manifest psychiatric disorders among caregivers (p
> 0.05 in all).
In the current study, the families that showed PSD (FSF score::;
27) had significantly lower mean value of socioeconomic score compared to families with fair
psychosocial function (p < 0.05). Also, the prevalence of very-low socio-economic level was higher
in the former subgroup compared to the latter (p :S 0.01). Otherwise, both groups did not show
significant differences concerning other studied variables including the prevalence and mean values
ofDAI score.
In conclusion, the current study showed the wide spectrum of neurological, behavioral, and
psychiatric disorders in the studied Egyptian sample of PKU. Such wide spectrum that highlights the
importance of establishment of a nationwide screening program
for PKU in Egypt aiming at diagnosis and implementation of dietary therapy as early as possible.
Also, it revealed the socioeconomic, psychosocial, and psycho-pathological characteristics of
their caregivers. Meanwhile, the value of implementing an educational intervention program for
caregivers of affected children in increasing their knowledge about the disease and possible means
of dealing with such children has been elucidated.