R. Longhi

Pattern reversal visual evoked potentials in phenylketonuria

SummaryThe pathogenesis of brain dysfunction in phenylketonuria (PKU) is still under investigation. Hyperphenylalaninaemia results in increased turnover of myelin. In order to demonstrate the derangement of myelinization in PKU we studied the visual evoked potentials (VEP) in 14 PKU patients and in 20 normal subjects. VEP findings were correlated with the metabolic control of the disease and with the electroencephalographic findings. VEP were more sensitive than the EEG in detecting a neurological dysfunction. VEP are influenced by dietary control and are normal only in children with good metabolic control.

Cholesteryl Ester Storage Disease: Risk Factors for Atherosclerosis in a 15-Year-Old Boy

Cholesteryl ester storage disease (CESD; McKusick 21500), an autosomal recessive inborn error of metabolism, is characterized by deficient activity of lysosomal acid lipase. This disorder, unlike the more dangerous expression of the deficiency state, Wolman’s disease, can allow patients to live a long time and may not be detected until adulthood, in spite of important biochemical abnormalities. One of these concerns the lipidaemic pattern and the related risk of developing early atherosclerosis due to a high serum total cholesterol and triglyceride levels coupled with very low high-density lipoprotein (HDL) values. As a consequence, a wide range of clinical pictures of the disease is possible, ranging from mild clinical expressions to life threatening ones. We describe here the case of a young subject affected by CESD, emphasizing the risk factors for the development of early atherosclerosis.

Cranial computerized tomography in dihydropteridine reductase deficiency

Dihydropteridine reductase deficiency is a rare cause of hyperphenylalaninaemia, characterized by severe and progressive neurological impairment, despite early and accurate dietary control of plasma phenylalanine. We describe two girls, diagnosed at 17 and 14 months of age, respectively, and immediately treated withl-dopa, 5-hydroxytryptophan and carbidopa. In spite of an adequate dietary and pharmacological treatment, the clinical and neurological pictures progressively worsened. Repeated cranial computerized axial tomography scans showed degeneration of the white matter and, in one case, calcification of the basal ganglia. The possible association of this last finding with folate depletion is discussed.

Serotonin and noradrenaline concentrations and serotonin uptake in platelets from hyperphenylalaninaemic patients

SummaryIn three untreated patients with phenylketonuria (PKU), three PKU and six hyperphenylalaninaemic (HPA) patients in good metabolic control, the kinetic constants of plateletin vitro uptake of [14C]serotonin (5HT) did not significantly differ from those in 12 control subjects matched for age. The platelet concentrations of endogenous 5HT and noradrenaline (NA), taken as long-term indices of the amount of these amines circulating in plasma, were lower than normal in PKU and HPA patients, whether or not they were kept on a diet. However, a reduction in plasma NA concentrations at the moment of blood collection was seen only in untreated PKU patients. These data indicate that there may be a chronic inhibition of 5HT and possibly of NA synthesis even in PKU or HPA subjects in good metabolic control, with normal psychomotor development and only slightly raised plasma phenylalanine levels.

Plasma chromium and manganese levels in treated PKU patients

Plasma chromium (Cr) and manganese (Mn) levels were measured in 16 phenylketonuric (PKU) children, 1-13 years old. All these children had been on a phenylalanine (Phe) restricted diet for at least 12 months. The diet was based on a Phe-free protein substitute and various amounts of low Phe products. No clinical signs of Cr or Mn deficiency were evident in any of the patients. The control population included 16 healthy subjects of comparable age on a normal diet. In all children, blood was drawn after a 12 h fast. The determinations were performed using atomic absorption spectrophotometry with electrothermal atomization (Davidson and Secrest, 1972; Halls and Fell, 1981). The difference between means was tested for significance by the unpaired Students r test. PKU patients had a mean plasma Cr concentration of 2.20ngmL -1 with a standard deviation (SD) of 1.36 compared with 2.79ngmL -~ (SD+0.90) for the controls. Plasma Mn values were 2.91 ngmL -1 (SD+1.42) in the PKU patients and 3.13 ngmL -1 (SD_+1.89) in the controls. These differences were not significant. Even if we consider only the PKU patients under strict metabolic control (5 subjects with mean plasma Phe values during the previous year of ~<8 mg dL -1) no significant differences can be seen. Utilizing tables of composition of foodstuffs, we calculated the approximate daily Cr and Mn intake of our patients. Cr intake, variable in relation to age at between 0.05 and 0.1 mgd -I, is within the limits of the recommended dietary allowances (RDA: 0.02--0.2 mg d-1) (Committee on Dietary Allowances, 1980) for the various ages. In contrast, Mn daily intake, variable with age between 0.66 and 1.5 mg d -1, is always lower, for every age group, than recommended (RDA: 1-5mgd -1) (Committee on Dietary Allowances, 1980). The difference is greatest in the oldest children. The most likely explanation for this finding is the high bioavailability of the Mn contained in vegetables and fruits, two very important components of a low Phe diet.

Magnesium-deficient rickets in a phenylketonuric patient on dietary treatment

Absolute or relative vitamin D deficiency is the most frequent cause of rickets in children. Many reviews have shown that rickets may appear in association with environmental conditions, wrong dietary habits, gastrointestinal diseases and drug administration. Magnesium deficiency is also an uncommon cause of rickets. We report the case of a phenylketonuric (PKU) child with vitamin D-resistant rickets and magnesium deficiency.

Effect of Granulocyte-Colony Stimulating Factor in Glycogen Storage Disease Type IB

Five children with glycogen storage disease type Ib (glycogenosis Ib), a metabolic defect associated with neutropenia and impairment of neutrophil function, were treated with granulocyte colony stimulating factor, a haemopoietic growth factor that induces a significant increase in polymorphonuclear leucocyte count in vivo. Recurrent bacterial or fungal infections were recorded in the three patients who had very low polymorphonuclear leucocyte counts. Experience at this centre indicates that the absolute number of polymorphonuclear leucocytes is more important than the alteration of their metabolic function in determining the susceptibility of the patients to infection. Granulocyte colony stimulating factor was effective at increasing polymorphonuclear leucocyte numbers (and restored function to some extent) in patients with glycogenosis Ib. This drug might be beneficial in cases of severe infection, in glycogenosis Ib patients with neutropenia.

Pubertal maturation and classical phenylketonuria.

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