Mutational spectrum of smith-lemli-opitz syndrome patients in hungary.

Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder characterized by multiple congenital abnormalities and mental retardation. The condition is caused by the deficiency of 7-dehydrocholesterol reductase (DHCR7) which catalyzes the final step in cholesterol biosynthesis. Biochemical diagnosis is based on increased concentration of 7-dehydrocholesterol (7-DHC) in the patient serum. Both life expectancy and quality of life are severely affected by the disease. The estimated prevalence of SLO syndrome ranges between 1:20,000 and 1:40,000 among Caucasians. Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases. These mutations show a large interethnic variability. There are no mutation distribution data from Hungary to date. Thirteen patients were diagnosed with SLO syndrome in our laboratory. As first-line tests, serum 7-DHC and total cholesterol were measured and, in positive cases, molecular genetic analysis of the DHCR7 gene was performed. Complete genetic background of the disease could be identified in 12 cases. In 1 case only 1 mutation was detected in a heterozygote form. One patient was homozygous for the common splice site mutation c.964-1G>C, while all other patients were compound heterozygotes. One novel missense mutation, c.374A>G (p.Tyr125Cys) was identified.

Minor physical anomalies in schizophrenia and bipolar affective disorder.

OBJECTIVE: The prevalence of minor physical anomalies (MPAs) (prenatal errors of morphogenesis) was evaluated in patients with schizophrenia and bipolar affective disorder. METHOD: A new modification of the Waldrop-scale was used to detect the presence or absence of 57 MPAs in 30 patients with schizophrenia, 30 with bipolar disorder, and in 30 matched normal controls. RESULTS: Patients with schizophrenia compared to normal controls had significantly higher rates of three minor malformations (furrowed tongue, flat occiput, primitive shape of ears) and those of one phenogenetic variant (wide distance between toes 1 and 2), and they also had a significantly higher rate of one minor malformation (primitive shape of ears), as compared to patients with bipolar disorder. In patients with bipolar disorder, furrowed tongue was significantly more common than in controls. CONCLUSIONS: These results support an 'early' neuro-developmental model of schizophrenia.

Polyunsaturated fatty acids in plasma lipids of obese children with and without metabolic cardiovascular syndrome.

Previously we reported significantly higher values of gamma-linolenic acid (GLA, 18:3n-6), dihomo-gamma-linolenic acid (DHGLA, 20:3n-6), and arachidonic acid (20:4n-6) in plasma lipid classes in obese children than in nonobese controls. In the present study, fatty acid composition of plasma phospholipids (PL) and sterol esters (STE) was determined by high-resolution capillary gas-liquid chromatography in obese children with and without metabolic cardiovascular syndrome [MCS: defined as simultaneous presence of (i) dyslipidemia, (ii) hyperinsulinemia, (iii) hypertension, and.(iv) impaired glucose tolerance] and in nonobese controls. Fatty acid composition of PL and STE lipids did not differ between obese children without MCS and controls. Obese children with MCS exhibited significantly lower linoleic acid (LA, 18:2n-6) values in PL (17.43 [2.36], % wt/wt, median [range from the first to the third quartile]) than obese children without MCS (19.14 [3.49]) and controls (20.28 13.80]). In contrast, PL GLA values were significantly higher in obese children with (0.13 [0.08]) than in those without MCS (0.08 [0.04]), whereas STE GLA values were higher in obese children with MCS (1.04 [0.72]) than in controls (0.62 [0.48]). DHGLA values in PL were significantly higher in obese children with MCS (4.06 [0.74]) than in controls (2.69 [1.60]). The GLA/LA ratio was significantly higher, whereas the AA/DHGLA ratio was significantly lower in obese children with MCS than in obese children without MCS and in controls. In this study, LA metabolism was affected only in obese children with but not in those without MCS. In obese children with MCS, delta6-desaturase activity appeared to be stimulated, whereas delta5-desaturase activity appeared to be inhibited. Disturbances in LA metabolism may represent an additional health hazard within the multifaceted clinical picture of MCS.

Urinary cortisol to cortisone metabolites in hypertensive obese children.

Childhood obesity is accompanied by a variety of cardiovascular risk factors (hypertension, insulin resistance, dyslipidaemia) which tend to aggregate (syndrome X). 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is supposed to play a role in the pathogenesis of hypertension and the development of syndrome X. There are two isoforms of 11beta-HSD. 11beta-HSD-2 is responsible for the inactivation of cortisol to inactive cortisone. In the case of impaired enzyme activity the ratio of urinary tetrahydrocortisol (THF)+ its isomer allotetrahydrocortisol (5alpha-THF)/tetrahydrocortisone (THE) is elevated. 11beta-HSD-1 is an oxo-reductase, which type catalyses the conversion of cortisone to cortisol. The aim of the present study was to investigate if there was any alteration in the urinary cortisol metabolites reflecting 11beta-HSD activity in hypertensive obese children (no.=15) as compared to normotensive obese (no.=11) and normotensive non-obese children (no.=15). We found an increased excretion of cortisol metabolites in hypertensive obese children compared to obese and normal - weight children having normal blood pressure. The ratio of THF+5alpha(THF/THE had a significant correlation with systolic blood pressure. On the basis of our study the ratio of THF+5alpha-THF/ THE reflecting on altered enzyme activity seems to be an independent factor influencing especially systolic blood pressure in hypertensive obese children.

Antipsychotics and breast-feeding: a review of the literature.

Many women with mental illnesses would like to breast feed their infants. In light of the limited but rapidly growing data, it seems that in some cases the possible physiological and psychological benefits may outweigh putative risks. All antipsychotics are secreted into breast milk but the concentrations and effects vary. There is a subgroup of mothers with mental illnesses who want to breast feed their infants and who are receiving a single established antipsychotic drug (principally, haloperidol or chlorpromazine) at the lowest possible clinically effective dose. As a tentative conclusion, this group could experience benefits from being able to nurse which would outweigh the risk of exposing their babies to very small amounts of antipsychotic drugs. However, larger study groups with longer follow-up periods would be required to confirm this tentative conclusion. Those mothers who require 2 or more antipsychotic drugs simultaneously and those taking one drug, but at the upper end of the recommended dose range, should not be advised to breast feed. Safety considerations suggest that women taking atypical antipsychotics would be advised not to breast feed because of the limited experience with these agents. When mothers taking antipsychotic drugs do nurse, it is desirable to monitor drug concentrations in breast milk and in the infants themselves. Close monitoring of the infant is essential.

Depressive symptoms among obese children.

The authors compare the appearance of depressive symptoms in 30 obese children in outpatient care and 30 normal-weight controls. The Montgomery-Asberg Depression Rating Scale showed a significantly higher rate of depression in the obese children (p < 0.01). The results are interpreted in the light of the partially contradictory views in the literature. Reference is also made to the therapeutic aspects of the problem.

Presence of metabolic cardiovascular syndrome in obese children.

UNLABELLED: The aim of the present study was to investigate the aggregation of cardiovascular risk factors (hyperinsulinaemia, impaired glucose tolerance, dyslipidaemia, and hypertension) in 180 (77 female, 103 male) obese and 239 control children. Blood glucose, serum insulin and lipid levels were determined from blood samples taken after an overnight fast. Oral glucose tolerance tests were performed and blood glucose concentrations were monitored. The body mass index, body fat (on the basis of skinfold measurements), lean body mass and waist/hip ratio were calculated and blood pressure was measured five times in all subjects. It was shown that only 14.4% of obese children were free from any risk factors, in contrast to 79.1% of the control children. Four risk factors (metabolic cardiovascular syndrome) were found in 8.9% of the obese children (8.7% in males and 9.1% in females) while none could be detected in controls. Considerable differences were also detected in the prevalence of one, two or three risk factors between control and obese children. Patients with the metabolic cardiovascular syndrome could not be characterized by any of the investigated anthropometric characteristics, but the duration of obesity was significantly longer in these children. CONCLUSION: Potential risk factors for cardiovascular diseases already tend to cluster in childhood and they are strongly associated with obesity. Our observations suggest that the development of the metabolic cardiovascular syndrome has its origin in childhood.

Informative morphogenetic variants in patients with schizophrenia and alcohol-dependent patients: beyond the Waldrop Scale.

OBJECTIVE: The authors evaluated the presence or absence of informative morphogenetic variants in patients with schizophrenia compared with alcohol-dependent patients. METHODS: Taking into consideration the criticisms of the Waldrop Scale, which was widely used until recently to define the presence of informative morphogenetic variants, the authors evaluated the presence or absence of 56 informative morphogenetic variants in 50 consecutively admitted patients with schizophrenia and 50 consecutively admitted alcohol-dependent patients. They made a distinction between minor malformations (those developing during organogenesis) and phenogenetic variants (those developing after organogenesis). A kappa index above 75% was considered reliable. RESULTS: Thirty-four of the 56 informative morphogenetic variants met the authors' reliability criterion. Patients with schizophrenia had significantly higher rates of three minor malformations (furrowed tongue, multiple buccal frenula, and hemangioma) and two phenogenetic variants (protruding auricle and large tongue). CONCLUSIONS: The results suggest that using finer distinction in the evaluation of informative morphogenetic variants in schizophrenia may open new perspectives in the research of the neurodevelopmental background of schizophrenia.

Urinary sodium excretion: association with hyperinsulinaemia, hypertension and sympathetic nervous system activity in obese and control children.

UNLABELLED: The aim of the present study was to evaluate the association between 24 h urinary excretion of sodium and blood pressure, fasting plasma insulin, renin, aldosterone and serum norepinephrine concentrations in 45 obese and 15 control children. Urinary sodium excretion was significantly lower in obese subjects (1.3 +/- 0.6 mmol/kg/24 h, P < 0.01) than in controls (2.8 +/- 1.3 mmol/kg/24 h). Hyperinsulinaemia did not affect sodium excretion of obese children. Plasma renin and aldosterone levels did not correlate with sodium excretion and were significantly higher in overweight children. Serum norepinephrine levels were also significantly higher in the obese group (0.66 +/- 0.89 microgram/100 ml) as compared to the controls (0.11 +/- 0.03 microgram/100 ml, P < 0.01) and showed significant negative correlation with urinary sodium excretion (r = 0.43, P < 0.05). CONCLUSION: Hyperinsulinaemia and the consequently increased sympathetic nervous system activity might be involved in the development of high blood pressure in obese children by decreasing urinary sodium excretion.

[Multi-metabolic syndrome in obese children]. / Multimetabolikus szindróma kövér gyermekekben.

The occurrence of multimetabolic syndrome was studied in 114 (63 boys, 51 girls) obese children. From the blood sample taken after on overnight fast blood sugar, serum insulin, and lipid levels were determined. During oral glucose tolerance test blood sugar concentrations were followed. Body mass index, body fat (on the basis of skinfold measurements), lean body mass and waist/hip ratio were calculated and blood pressure was measured 6 times in all subjects. Multimetabolic syndrome was found in 16% of boys and 19.6% of girls. No significant sex difference in the frequency of multimetabolic syndrome was found. Patients with multimetabolic syndrome could not be characterized by high waist/hip ratio any other antropometric parameter. The duration of obesity was significantly higher in subjects with multimetabolic syndrome than in those not suffering from the syndrome. This finding supports the hypothesis that the development of the multimetabolic syndrome is a process. The authors emphasize the significance of this problem and the importance of early recognition and prevention.