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Phenylketonuria (PKU) is a congenital metabolic autosomic recessive disease, caused by a deficit in the liver of phenyl-alanine hydroxylase, the enzyme responsible for conversion of phenyl-alanine (PHE) into tyrosine. Reduction of this enzymatic activity is responsible for increased phenyl-alanine in blood and tissues and, above all, in brain. Accumulation of PHE causes neural damage which produces a typical clinical picture with mental retardation, psychiatric symptoms and epilepsy. It is now possible to diagnose this disease early (with neonatal screening), before irreversible clinical symptoms reflecting central nervous system injury appear. Early diagnosis allows timely onset of therapy (the only possible) consisting of a special diet with reduced intake of PHE (integrated with a mix of aminoacids) whose objective is to keep levels of PHE low in the blood (3–6 mg/dl). Magnetic Resonance Imaging (MRI) is the elective diagnostic tool to evaluate in vivo the involvement of the brain in PKU. Previous MRI morphological studies in patients with PKU have reported various focal symmetrical lesions in periventricular white matter (especially parieto-occipital) of patients with PKU with PHE blood values higher than 10 mg/dl. These lesions, whose importance is not yet clear, seem to represent a reversible structural alteration of myelin, since they regress if blood PHE decreases. Proton magnetic resonance spectroscopy (1H-MRS) can measure in vivo brain metabolites which could help determine the nature of white matter lesions. In particular, changes in NAA (a marker of neuronal integrity) or mI (a potential astrocytic marker) could point to possible neurochemical dysfunction, whereas Cho levels may parallel the degree of the tissue myelination. The purpose of the present study was to evaluate morphologically and biochemically the regional specificity of white matter lesions with structural MRI and with 1H-MRSI. The study included 12 patients with PKU ten to 42 years of age. All patients underwent structural MRI scans while eight of them were also studied with 1H-MRSI. Structural MRI lesions in white matter were analyzed both qualitatively (signal intensity) and quantitatively (location and extension). 1H-MRSI metabolites were measured as the ratio of the area under each peak: NAA/Cr, NAA/Cho, Cho/Cr. Analysis of location and extension of the lesion on structural MRI data showed limited involvement of parieto-occipital white matter in three cases (with isointense or vaguely hypointense lesions in T1, and moderately hyperintense lesions in T2); medium involvement in six cases (with fairly hypointense or isointense lesions in T1, fairly or moderately hyperintense lesions in T2); serious involvement in three cases (with isointense or fairly hypointense lesions in T1, and fairly hyperintense lesions in T2). As for 1H-MRSI data, ANOVA showed a significant reduction of NAA/Cho and increase in Cho/Cr in white matter lesions, but no change in NAA/Cr. No correlation was found between clinical parameters and morphological or spectroscopic data. In conclusion, our morphological MRI data confirmed the presence of multiple signal alterations, focal and symmetrical, in deep periventricular white matter (especially posterior), with occasional involvement of subcortical white matter. However, these lesions do not seem to be strongly predictive of clinical outcome. 1H-MRSI data suggest increased Cho levels in white matter lesions. Since Cho is thought to reflect membrane turnover, these data may support the demyelinating nature of lesions, consistent with earlier post mortem studies.

Objective: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. Methods: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. Results: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues λmin, λmiddle, λmax obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient’s age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). Conclusions: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

In this paper, discrepancies and reference inaccuracies in the paper (Grana , 2003) are pointed out. Specifically, it is demonstrated that the definitions of "lesion gradient" and "skin lesion gradient," widely used in a number of medical papers on computer analysis of pigmented skin lesions, are unambiguous, and that the "new algorithm for border description" described in the subject paper substantially relies on well-established concepts dating back over one decade ago

The authors discuss their experience regarding the three-dimensional reconstruction of the echographic image, firstly of an orbital angioma and secondly, of a malignant choroidal melanoma. Of the latter, they calculate the volume and the total external surface. Reference is also made to data regarding reproducibility, the errors of reconstruction methodology and volume calculation. However, it is more reliable than the commonly used echographic procedures.

As already described for cystic fibrosis and Friedreich ataxia, the incidence of PKU in Italy has been estimated by determining the increase of consanguineous marriages among 178 couples of PKU parents over the frequencies carefully established for the same marriages in the general Italian population for each of the 95 provinces during a 55-year period. The incidence estimated (between 1/15595 and 1/17815 according to two different formulas) is not very different from the incidence derived from screening programs (almost 1/12000). This indicates that the former method can be applied in Italy to the study of the incidence of other autosomal recessive disorders.