1.0 0.5 0 –0.5 –1.0 –1.5 –2.0 –2.5 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 2.5 2.0 1.5 1.0 0.5 0 –0.5 –1.0 –1.5 –2.0 Bone mineral density in patients with phenylketonuria 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 FN_Z-score_2007 FN_Z-score_2009 FN_Z-score_2007 FN_Z-score_2009 Figure 1. Femoral Z-score at baseline and follow-up Figure 2. Lumbar Z-score at baseline and follow-up addition to diet control and showed an improvement of their BMD Z-score from –1.7, –1.63, –1.29, –1.50, and –1.10 in the first evaluation to – 0.43, –0.76, –0.41, –1.17, and –0.72 in the second evaluation. Only one patient remained osteopenic. The rest of osteopenic patients refused to take the drug supplement and showed a slower rate of improvement from –2.02, 1.56, –1.01, –1.42, –1.63 to –1.05, –1.22, –0.7, –1.2, –1.4. Four patients remained in the osteopenic region. Clinically, there was a delay in the different developmental milestones in the group of patients, with mean age of head support 1.2 ±0.93 years, age of mother recognition 1.6 ±1.6 years, age of sitting 1.3 ±0.95 years, age of walking 2.6 ±1.3 years. The duration of diet compliance (mean 2.3 ±2.1 years) was associated with a significant inverse negative correlation with the blood phe level both at the start and follow-up (r = –0.05, p < 0.001 and r = –0.05, p < 0.005) respectively. The mean age of diagnosis was 1.8 ±1.4 years (1 week-4 years); 9 patients were diagnosed early (the first 6 months of life); 5 of them were diagnosed in the neonatal period (positive history in a sib); 4 of those 5 were on a strict low protein diet and are mentally normal, attending regular schools. Concerning the pattern of patient compliance, 11 of them (34.37%) were not compliant (off diet), 12 (37.5%) were partially compliant with some period of relaxation (irregular pattern) and 9 (28.12%) had a strict continuous pattern of compliance. The age of speech for the 3 groups was: no speech present in the off-diet group (only a few words), 1.8 ±0.40 years in the irregular group and 2 ±0.78 years in the continuous group. The blood phe levels showed a significant statistical difference between the 3 groups, where the smallest value was in the continuously compliant group; in 2007 the mean was 16.4 ±1.15 mg/dl in the off group, 13 ±0.94 mg/dl in the irregular group and 6.3 ±1.2 mg/dl in the continuously compliant group (F-ratio = 20.572, p ≤ 0.0001). In 2009, the mean was 14.6 ±1.32 mg/dl in the off group, 14.2 ±1.01 mg/dl in the irregular group and 4.9 ±0.75 mg/dl in the continuously compliant group (F-ratio 23.214, p ≤ 0.0001). A marked improvement of milestones and symptoms with diet (as reported by the patients) was noted in the compliant groups, both irregular and continuous (e.g. mother recognition, sitting, walking, and speech). No statistically significant difference was found between the 3 groups regarding the femoral and lumbar BMD and BMC together with their Z-scores. Neurological examination at the start of the study was normal in most patients apart from hypotonia, which was detected in only one patient (3.33%), hypertonia in 4 patients (12.5%) and exaggerated knee jerk in only one patient (3.33%). These signs disappeared by the end of the study except the hypotonia, which remained in the same patient (off diet). Examination of other systems revealed no abnormality. Discussion With any dietary manipulation involving elimination of key nutrients as in PKU it is essential that the replacement therapy is adequate to ensure normal growth and that the patients are monitored long term for adverse effects [2]. Our results confirmed the reduced bone mineralization in children and adolescents with PKU compared with controls as reported by other authors [2, 7, 9, 11-13], who confirmed the lower BMD in children and adolescents with classical PKU on a standard dietary regime. The mean femoral and lumbar BMD Z-scores were significantly lower than the controls and osteopenia was detected in 31.25% of our patients in the femoral neck. These findings were similar to those of Modan-Moses (2007) [13], who found osteopenia in at least one skeletal site in 38.7% of his patients and reported that trabecular bone mass as represented by the femoral neck density was severely affected. In contrast to the findings of Modan-Moses [13] none of our patients Arch Med Sci 3, June / 2011 497