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Background: Serious hematological, metabolic and neurological complications owing to the nutritional deficiency of vitamin B12 may occur in infants of mothers on a strict vegetarian diet., Methods and Results: The mother of the first child was a strict vegetarian. She had an elevated urinary methylmalonic acid level and a low concentration of serum vitamin B12. Her 13-month-old daughter was exclusively breast-fed until the age of 9 month and then she was fed only vegetables. Physical examination revealed psychomotoric retardation, apathy, muscular hypotonia, abnormal movements and failure to thrive. Laboratory analysis showed a megaloblastic anaemia, a low level of vitamin B12 and methylmalonic aciduria. MRI of the brain revealed diffuse frontotemporoparietal atrophy and retardation of myelination. After treatment with vitamin B12 supplements, abnormal movements disappeared and development improved, but a mild generalised hypotonia continued. A cranial MRI 9 months after treatment still showed signs of retardation of myelination. The second patient, an 8 month-old male, son of a strict vegetarian mother too, was referred for investigation of psychomotoric retardation, hypotonia, dyskinesia, failure to thrive and microcephaly. He was breast-fed and from 6 month of age he had also received fruit juices. Laboratory analysis revealed megaloblastic anaemia, high methylmalonic aciduria and homocystinuria. The patient's and his mother's serum level of vitamin B12 were low. After treatment with vitamin B12 supplements, biochemical and metabolic markers of disease were normal but there continued a generalised hypotonia, microcephaly and language delay., Conclusion: Our observations emphasize the health complications of nutritional cobalamine deficiency and a requirement of clinical, biochemical and metabolic monitoring in infants within strict vegetarian families.

Background: Homocystinuria due to cystathionine beta-synthase deficiency is an autosomal recessive disorder of methionine metabolism. It manifests with vascular, central nervous system and connective tissue disturbances, and phenotypically resembles Marfan's syndrome. We analysed the clinical course of homocystinuria in Czech and Slovak patients., Methods and Results: The group of homocystinuric patients consisted of 19 individuals (12 males and 7 females) aged 5-32 years (average age 18 years), who were diagnosed between 1980 and 1999. The overall incidence of homocystinuria in the Czech and Slovak Republics was 1:287,000. The proportion of pyridoxine-responsive patients was 47%. The average follow-up period was 10 years (range 1 month to 19 years). The prevalence of the individual signs in the group was as follows: lens dislocation--95% of patients, progressive myopia--79%, marfanoid habitus--74%, kyfoscoliosis--68%, osteoporosis--63%, psychomotor retardation--58%, other neurologic symptomatology--58% and tromboembolism--21%. The average delay between the first sign of the disease and the time when the diagnosis was made was 4 years (range 1 to 14 years). At the time of diagnosis the average levels of metabolites in plasma were as follows: total homocysteine 348 mumol/l (range 211-536), free homocystine 70 mumol/l (range 0-203) and methionine 359 mumol/l (range 75-937)., Conclusions: Both the clinical course of homocystinuria due to the cystathionine beta-synthase deficiency and its incidence in the Czech and Slovak Republics are similar to those in other populations. Since homocystinuria is a treatable disease, it should be included in the differential diagnosis of Marfan's syndrome, tromboembolism and severe psychomotor retardation.

Background: Prenatal diagnosisi represents the important fprm of prevention of the inherited metabolic diseases and its accessibility becomes the most effective assistance to involved families. The aim of the study was to introduce prenatal diagnosis of major inherited lysosomal disorders of the group of lipidoses, micopolysaccharidoses, glycoproteinoses, and mucolipidoses., Methods and Results: Methodological approach is based on the activity estimation of the specific lysosomal hydrolases that are missing or inactive. Methods were extended by a set of supportive analyses, namely by ultrastructural identification of the lysosomal storage of the non-degraded substrate, DNA analysis showing mutation in the family or by biochemical analysis of the amniotic fluid. Uncultured cultured chorionic villi, cultured amniotic fluid cells yand samples of the amniotic fluid were examined. Altogether 17 pregnancies at risk for seven different lysosomal enzymopathies were followed: GM2 gangliosidosis (2 cases), Fabra disease (3 cases), Krabbe disease (1 case), Niemann-Pick disease type A (1 case), mucopolysaccharidosis I (5 cases), mucopolysaccharidosis II (4 cases), mucolipidosis II (I-cell disease) (1 case). Profound deficiency of enzyme activities (alpha-galactosidase A in fabry disease, galactocerebrosidase in Krabbe disease, alpha-iduronidase in mucopolysaccharidosis I) was identified in three pregnancies, which were terminated on the mother's decision. The diagnose was confirmed by the biochemical analysis of tissues of aborted foetuses. In two of them (Fabry disease, mucopolysaccharidosis I) ultrastructural sings of storage werw proved. In two cases the foetal heterozygote state was identified. In case at risk for Niemann-Pick disease type A, the diagnosis was confirmed also by DNA analysis. In the pregnancy at risk for Fabry disease, heterozygous state was confirmed indirectly according to the difference of alpha-galactosidase activities in cultured and uncultured cells. A set control values of enzyme activities in individual types of processed material (native and cultured chorionic villi, cultured amniocytes, and amniotic fluid supernatant) has been established., Conclusions: Inherited lysosomal enzymopathies represent important indication for prenatal diagnosis available now in our department. Condicio sine qua non is the biochemical or molecular genetic confirmation of diagnosis in the family involved.

Background: A rise of the homocysteine plasma level--mild hyperhomocysteinaemia--is considered an independent risk factor for the development of vascular damage. It is due to hereditary deficiency of 5,10-methylene-tetrahydrofolate reductase with accentuation of vitamin deficiency (folic acid, vitamin B6 and B12). In previous studies the authors confirmed this fact in the population of patients with aortocoronary or peripheral arterial bypasses. The assumed autosomal recessive transmission of this deficiency should make it possible to detect carriers of this metabolic deviation already in childhood. By selective screening of the child population at risk it would thus be possible to detect affected subjects in time and prevent the development of vascular disease by preventive folate administration., Methods and Results: In a group of 38 children and grandchildren from risk families where at least one of the parents or grandparents was operated on account of vascular obliterating disease the total homocysteine plasma level was examined by the chromatographic method. An increase of total homocystein (8.7 +/- 2.7 mumol/l) was found as compared with children from the non-risk population (5.4 +/- 1.8 mumol/l), (p < 0.001). The total homocysteine values however were dependent on the child's age and were more marked in children above 12 years of age. In the parental population mild hyperhomocysteinaemia was present in 38% of those with aortocoronary bypasses and in 43% of those with peripheral arterial bypasses., Conclusions: The authors found significantly elevated total homocysteine levels in the child population from risk families with obliterating vascular disease. The total homocysteine level depends on the child's age and is more markedly expressed in children above 12 years of age.

Background: Elevated total homocysteine plasma levels are considered a significant factor of vascular damage. As they are encountered in more than half the patients with atherosclerotic vascular damage the importance as a lipid-dependent or lipid-independent risk factor in the promotion of pathophysiological processes is discussed., Methods and Results: In a group of 100 healthy subjects and 529 patients with indication for an aortocoronary or peripheral arterial bypass and in patients from the lipid clinic the mutual relation between total plasma homocysteine levels and selected indicators of the lipid metabolism was investigated. The following results more obtained: for total cholesterol a correlation coefficient of r = 0.26, for HDL-cholesterol r = 0.20, for LDL-cholesterol r = 0.21, for triacylglycerols r = 0.29, apolipoprotein A-I r = 0.06, apolipoprotein B r = -0.12 and for Lp(a) r = -0.03. To ensure correct evaluation of the homocysteine levels simultaneously also folate levels were examined (correlation coefficient r = 0.28), vitamin B12 r = (0.03) and fibrinogen r = (0.09)., Conclusions: The authors did not detect an unequovical relationship between the total homocysteine level and selected lipid indicators in any of the patient groups (p < 0.05).

Background: Elevated phenylalanine levels in maternal blood (hyperphenylalaninaemia) during pregnancy damages the developing foetal tissues. Early detection of pregnant women with hyperphenylalaninaemia and adherence to a low phenylalanine diet already before conception and throughout pregnancy can prevent this damage. The objective of the investigation are results achieved screening and strict monitoring of low phenylalanine dietetic treatment in detected pregnant women of the Prague population., Methods and Results: 186 350 healthy women of the Prague population were examined by the chromatographic screening test in a venous blood sample during their first visit in a maternity welfare centre and 22 positive cases were detected (incidence 1:8470). In 86% mild, persistent or benign forms of phenylketonuria were involved. Nineteen patients were treated by a low phenylalanine diet and the phenylalanine tolerance was monitored as well as the nitrogen balance, amino acids in serum and urine, protein markers, trace elements, vitamins, lipids, the body mass index-BMI, changes of body weight after introduction of the dietetic treatment and treatment during pregnancy. A significant increase of the phenylalanine tolerance by 20 to 200% was found, mostly in the second half of pregnancy and reduced values of serum and urinary selenium. The decrease of body weight when the diet was introduced and the increment during pregnancy correlated with the BMI value. In the other investigated parameters no significant deviations were found., Conclusion: Fifteen healthy children with normal psychomotor development delivered by 12 mothers with hyperphenylalaninaemia provide evidence of the effectiveness of prenatal screening for hyperphenylalaninaemia during pregnancy.