Clinical and neuropsychological outcomes for children with phenylketonuria in Upper Egypt; a single-center study over 5 years

Figures & data

Table 1 Distribution of the studied children by sociodemographic and disease-related criteria

Patient characteristics	N (%)
Gender
Male	69 (61.1)
Female	44 (38.9)
Age at presentation
<2 years	48 (42.5)
2–5 years	38 (33.6)
>5 years	27 (23.9)
Residence
Urban	26 (23)
Rural	86 (77)
Consanguinity
Positive	96 (85)
Negative	17 (15)
Family history
Positive	47 (41.6)
Negative	66 (58.4)
Weight
Mean ± SD	15.3±8.4
Head circumference
Mean ± SD	46.3±3.6
Motor development
Normal	51 (45.1)
Delayed	62 (54.9)
Speech development
Normal	2 (1.8)
Delayed	111 (98.2)
Social development
Normal	4 (3.5)
Delayed	109 (96.5)
Duration of nutritional therapy (months)
Mean ± SD	35.01±27.5

Figure 1 Relative frequency of the presenting manifestations among the studied PKU patients.

Note: Cases may have 1 or more complaints (N=113).
Abbreviation: PKU, phenylketonuria.

Figure 2 Distribution of the studied PKU children according to time of diagnosis (N=113).

Abbreviation: PKU, phenylketonuria.

Table 2 Neurological examination and investigations done for the studied children

Neurological examination and investigations	N (%)
Neurological examination
Hypertonia, hyperreflexia	2 (1.8)
Hypotonia, hyperreflexia	50 (44.2)
Normal	61 (54)
CT
Brain atrophic changes	39 (34.4)
White matter changes	2 (1.8)
Normal	23 (20.4)
Not done	49 (43.4)
MRI
Brain atrophic changes	4 (3.5)
White matter changes	13 (11.5)
Normal	3 (2.7)
Not done	93 (82.3)
EEG
Hypsarrhythmia	9 (8)
Generalized epileptic discharges	24 (21.2)
Focal epileptic discharges	10 (8.8)
Normal	14 (12.4)
Not done	56 (49.6)
Metabolic screening (blood Phe in μmol/L)
Mean ± SD	1,212±546
Classification
Hyperphenylalaninemia	18 (15.9)
Mild to moderate PKU	40 (35.4)
Classical PKU	55 (48.7)

Abbreviations: CT, computed tomography; EEG, electroencephalography; MRI, magnetic resonance imaging; PKU, phenylketonuria.

Table 3 Distribution of the studied children according to the developmental outcome

Characteristics	N (%)
Motor outcome
Normal	52 (46)
Good	38 (33.6)
Poor	23 (20.4)
Language outcome
Good	17 (15)
Poor	96 (85)
Social outcome
Good	17 (15)
Poor	96 (85)
Behavioral outcome
Good outcome	5 (4.4)
Poor outcome	108 (95.6)
Presence of seizures
No	89 (78.8)
Yes	24 (21.2)
Control of seizures (seizures outcome)
No convulsions	89 (78.8)
Controlled	16 (14.1)
Uncontrolled	8 (7.1)
Overall IQ
Mean ± SD	49.08±10.04
Verbal IQ
Mean ± SD	47.88±9.72
CARS
Mean ± SD	30.74±7.002
CAAS
Mean ± SD	59.42±5.61

Abbreviations: CAAS, Children’s Attention and Adjustment Survey; CARS, Childhood Autism Rating Scale; IQ, intelligence quotient.

Table 4 Psychometric evaluation of the studied patients

Category	N	%
Overall IQ
90–109 (average)	1	0.9
80–89 (low average)	0	0.0
70–79 (borderline impaired or delayed)	7	6.2
55–69 (mildly impaired or delayed)	18	15.9
40–54 (moderately impaired or delayed)	87	77
Verbal IQ
90–109 (average)	1	0.9
80–89 (low average)	1	0.9
70–79 (borderline impaired or delayed)	5	4.4
55–69 (mildly impaired or delayed)	12	10.6
40–54 (moderately impaired or delayed)	94	83.2
CARS scores
15–29.5 (minimal to no symptoms)	56	49.6
30–36.5 (mild-moderate autism)	39	34.5
≥37 (severe autism)	18	15.9
CAAS
<40 (low probability)	0	0
40–49 (below average)	6	5.3
50–59 (average)	45	39.8
60–69 (super average)	55	48.7
≥70 (severe)	7	6.2

Abbreviations: CAAS, Children’s Attention and Adjustment Survey; CARS, Childhood Autism Rating Scale; IQ, intelligence quotient.

Table 5 Sociodemographic and disease-related criteria of patients with regard to different outcomes of motor function groups

Parameter	Outcome			P-valuea
	No motor affection (N=52)	Motor affection with good outcome (N=38)	Motor affection with poor outcome (N=23)
Gender
Male	34 (65.4%)	26 (68.4%)	9 (39.1%)	0.052
Female	18 (34.6%)	12 (31.6%)	14 (60.9%)
Age at presentation
<2 years	5 (9.6%)	28 (73.7%)	15 (65.2%)
2–5 years	24 (46.2%)	9 (23.7%)	5 (21.7%)	<0.001
>5 years	23 (44.2%)	1 (2.6%)	3 (13.1%)
Family history
Positive	24 (46.2%)	10 (26.3%)	13 (56.5%)	0.045
Negative	28 (53.8%)	28 (73.7%)	10 (43.5%)
Classification
Hyperphenylalaninemia	10 (19.2%)	3 (7.9%)	5 (21.7%)
Mild to moderate PKU	20 (38.5%)	13 (34.2%)	7 (30.4%)	0.434
Classical PKU	22 (42.3%)	22 (57.9%)	11 (47.9%)
Duration of nutritional therapy (months)
Mean ± SD	39.86±33.23	32.92±20.71	27.52±21.41	0.412
White matter and brain atrophic changes by CT or MRI brain (n=71)
No	18 (75%)	5 (17.2%)	2 (11.1%)	<0.001
Yes	6 (25%)	24 (82.8%)	16 (88.9%)

Note:

a Statistically significant difference (P<0.05).

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PKU, phenylketonuria.

Table 6 Logistic regression analysis of predictor variables of poor motor and language outcome

Characteristics	OR (95% CI)	P-valuea
Univariate binary logistic regression analysis of predictor variables of poor motor outcome
Gender
Female	3.1 (1.2–8.01)	0.019a
Male	1
Abnormal imaging findings
Yes	6.1 (1.3–29.4)	0.023a
No	1
Characteristics	Adjusted OR (95% CI)	P-value
The final model of stepwise binary logistic regression analysis of predictor variables of poor motor outcome
Abnormal imaging findings
Yes	6.6 (1.2–35.6)	0.027a
No	1
Family history
Positive	3.1 (1.02–9.4)	0.045a
Negative	1
Characteristics	OR (95% CI)	P-value
Univariate binary logistic regression analysis of predictor variables of poor language outcome
Abnormal imaging findings
Yes	8.6 (1.6–45.2)	0.011a
No	1

Note:

a Statistically significant difference (P<0.05).

Abbreviations: CI, confidence interval; OR, odds ratio.

Figure 3 Frequency of WMA and brain atrophic changes among PKU patients in relation to various motor function group outcomes.

Abbreviations: PKU, phenylketonuria; WMA, white matter abnormalities.

Figure 4 Motor function outcomes with regard to the age of the patients.