Carnitine concentrations in term and preterm newborns at birth and during the first days of life.

Carnitine plays an important role in energetic metabolism. The aim of the study was to characterize the carnitine status in term and preterm newborns with respect to gestational age, birth weight, haematocrit and red blood cell count (RBC). The effect of nutrition on carnitine levels in the first week of life was also studied. Total blood pool of free carnitine (FC), acylcarnitines (AC) and total carnitine (TC) were analysed in whole cord blood and postnatally in capillary blood obtained at the day 4-6 in 33 term newborns and at the day 7-10 in 27 preterm newborns using tandem mass spectrometry. Plasma level of carnitine in the cord blood was measured using radioenzymatic method. Cord plasma levels of FC, AC and TC were higher in preterm newborns in comparison with term newborns (p < 0.01), but the total blood pool of FC and TC in whole cord blood was lower in preterm newborns than in term newborns (p < 0.01) and positive correlation was found between FC and gestational age or birth weight (p < 0.05). In addition, positive correlation was found between AC and red blood cell count or haematocrit (p < 0.05). During the first week of life, blood pool of FC and TC in term newborns and AC and TC in preterm newborns decreased regardless of the type of enteral or parenteral nutrition. Our results indicate that preterm newborns are born with limited carnitine store. Interpretation of carnitine analyses in whole blood relies in addition to gestational age and birth weight on the haematocrit, especially in newborns with anaemia or blood hyperviscosity.

Biochemical and molecular analyses in three patients with 3-hydroxy-3-methylglutaric aciduria.

Two methods, spectrophotometry and HPLC, were compared in the analyses of 3-hydroxy-3-methylglutaryl-CoA lyase (HL) activity in three unrelated Czech patients with 3-hydroxy-3-methylglutaric (HMG) aciduria and their family members. The HL activities in cultured fibroblasts and/or isolated lymphocytes of probands were below the detection limits of the methods used. Both methods were also suitable for recognition of all heterozygotes in affected families. We searched for pathogenic mutations in the HL gene. Molecular analyses revealed that two patients are homozygous for known mutation H233R and R41Q, respectively, whereas the third patient is a compound heterozygote for the mutation H233R and a novel mutation Pro9fs(-1). This study expands the knowledge of the genotypic variability of the HMG aciduria.

Mutation analysis of the GALT gene in Czech and Slovak galactosemia populations: identification of six novel mutations, including a stop codon mutation (X380R).

A study of the galactose-1-phosphate uridyltransferase (GALT) gene from 37 unrelated galactosemia families is reported here. A total of 16 sequence variations in eleven mutated alleles was found. The two most common molecular defects were the mutations Q188R (46.0%) and K285N (25.7%). Six novel mutations in the GALT gene, X380R, Y209S, E340K, L74fsdelCT, Q169K and L256/P257delGCC, were detected. Three mutations, V151A, L195P and R204X that were previously described in other populations, were also found. The mutation X380R, which breaks the stop codon of the GALT gene, causes elongation of the GALT enzyme's protein chain. A deletion of four nucleotides in the 5' promoter region, in a position 116 - 119 nucleotides upstream from the initiate codon (5'UTR-119delGTCA), was revealed in Duarte (D2) alleles, in addition to N314D, IVS4nt-27g-->c, IVS5nt+62g-->a, and IVS5nt-24g-->a. An unusual molecular genotype was observed on 2 types of classical galactosemia alleles, with six variations from the normal nucleotide sequence presented in cis (mutation V151A or E340K plus five Duarte (D2) characteristic variations). In summary, galactosemia is a heterogeneous disorder at the molecular level, and mutation N314D, appears to be an ancient genetic variant of the GALT gene. Hum Mutat 15:206, 2000.