Ozalp I

Inherited metabolic disorders in Turkey

SummaryA high prevalence of inherited metabolic diseases is present in Turkey; at least in part, this is due to consanguineous marriages.

Mutation analysis in Turkish phenylketonuria patients.

Forty-four classical PKU patients have been screened for various mutations. The newly identified IVS 10 splicing mutation was found in 32% of the mutant alleles and comprises 74.5% of the mutations that could be typed: 261arg-gln (6.8%), 158arg-gly (2.3%), 252arg-trp (1.1%), 280glu-lys (-), and 272gly-stop (-) were the other mutations that were screened.

A case of Pearson syndrome associated with multiple renal cysts.

A 41-day-old infant who had severe metabolic acidosis, anemia, bleeding, hypoglycemia, and proximal tubulopathy was diagnosed with Pearson syndrome. Fibrosis in the liver, severe iron deposition in hepatocytes, and multiple renal cortical cysts were found on postmortem examination. Southern blot analysis of mitochondrial DNA obtained from peripheral blood revealed a heteroplasmic deletion of approximately 3.5 kilobases.

Novel mutations cause biotinidase deficiency in Turkish children

Mutation analysis was performed on DNA from 31 Turkish children with profound biotinidase deficiency who were symptomatic or ascertained by newborn screening. The 98G:del7ins3 mutation is common in clinically ascertained children in both the United States and Turkish populations, but a unique common mutation, R79C, is found only in the Turkish children identified both clinically and by newborn screening. Another frequently occurring mutation, T532M, is only observed in the Turkish newborn screening group. There are four other less frequent novel mutations identified in the Turkish population. Interestingly, the Q456H and the A171T:D444H double mutation, which are the most common mutations found in the US newborn screening population and have not been observed in symptomatic children, do occur in clinically ascertained children in the Turkish population, although the double mutation may be associated with milder and/or later-onset symptoms.

Screening for congenital hypothyroidism in Turkey

AbstractA pilot study was performed to determine the incidence of congenital hypothyroidism (CH) in Turkey and to build a model for nationwide screening. From December 1991 to December 1992, 30097 newborns were screened for CH using a primary measurement of thyroid stimulating hormone in capillary blood on days 3–5 of life. Samples were obtained in collaboration with the ongoing nationwide phenylketonuria screening programme. Eleven cases of primary CH were detected giving the incidence of 1∶2736. Recall rate was 2.3%. Replacement therapy withl-thyroxine was started after the confirmation of diagnosis. The median age at the initiation of replacement therapy was 23 days (range 7–35 days).ConclusionThe incidence of CH is notably higher in Turkey than reported in most other countries. Iodine deficiency and/or dyshormonogenesis might contribute to this high incidence. This result emphasizes the necessity of a nationwide screening programme.

Study of 12 mutations in Turkish cystic fibrosis patients

67 unrelated cystic fibrosis (CF) patients were screened for some of the most common mutations of the CFTR gene. This analysis resulted in the identification of 34.6% of all CF alleles. The most common mutation is delta F508 (28.4%). Two other mutations account for a further 6.7% of the alleles (R347H: 3.0%; N1303K: 3.7%). 1677delTA, G542X, G551D, S549N/I, R553X, L558S, R334W, and R297Q were not detected.

The effect of zinc-supplemented bread consumption on school children with asymptomatic zinc deficiency

BACKGROUND Zinc deficiency has been seen in developing countries in which grain-based vegetable protein is consumed more often than animal protein. This study was done to emphasize the importance of zinc-fortified foods and to investigate bioavailability of zinc in zinc-fortified bread. METHODS Serum zinc concentrations in healthy 7- to 11-year-old school children were determined. In 24 of 101 children serum zinc concentrations were below 65 micrograms/ul. These 24 children with asymptomatic zinc deficiency were divided into two equal groups. The 12 children with low serum zinc concentrations received the zinc-fortified bread providing 2 mg/kg/day elemental zinc acetate for 90 days (zinc-supplemented group), whereas the other 12 children received the same quality bread with no zinc fortification (control group). RESULTS By the end of the period, the zinc-supplemented group had significantly higher serum and leukocyte zinc concentrations (p < 0.01) and the weight, serum albumin levels, and alkaline phosphatase increased (p < 0.01). Immune functions improved, evidenced by conversion of delayed hypersensitivity skin reactions. Zinc-fortified bread (2 mg/kg/day) caused no side effects or manifestations of zinc toxicity. CONCLUSIONS The results indicate that the bioavailability of zinc in the bread is satisfactory. The use of zinc-fortified bread was found to be an economical and readily accessible method to eliminate zinc deficiency and to prevent further occurrence.

DNA haplotype analysis at the phenylalanine hydroxylase locus in the Turkish population

SummaryThirty-nine Turkish phenylketonuria (PKU) families were investigated for their DNA haplotypes at the phenylalanine hydroxylase (PAH) locus. There was a threefold higher incidence of consanguinity in the population studied compared with the general Turkish population. The PAH DNA haplotype 6 was found to be almost exclusively associated not only with the mutant PAH genes but also with the classic phenotype in 39% of the Turkish patients. This haplotype was of no importance in northern European populations. The two DNA haplotypes (1 and 4) that were almost equally frequent among the normal and the mutant PAH genes in northern European populations show virtually the same distribution in Turkish individuals. In all populations studied, these haplotypes are associated with different phenotypes.

Incidence of phenylketonuria and hyperphenylalaninaemia in a sample of the Turkish newborn population

The incidence of hereditary aminoacidopathies has been determined and nationwide programmes focussed on the most common diseases have been set up in the USA and most of the European countries. Specifically, the programme for phenylketonuria (PKU, McKusick 26160) has been successful and has served as a model for the detection and preventive treatment of genetic diseases.

Valproate-induced lethal hyperammonaemic coma in a carrier of ornithine carbamoyltransferase deficiency

and 19 hours of peritoneal dialysis. The latter was accomplished by the insertion of a polyurethane catheter with a guide wire and the infusion of 25 ml/kg of 1.5% glucose dialysate per hour that was subsequently drained for 10 minutes. A total of 158mg of glycine (mean 8.3 rag/h) was removed by peritoneal dialysis. The plasma gtycine was reduced to 11.2mg/dl; thus our concerted efforts resulted in a marked reduction of plasma glycine, which still remained elevated. The clinical symptoms persisted, the EEG deteriorated and the neonate died. It is possible, however, that earlier institution of peritoneal dialysis in combination with drug administration, e.g. benzoate or strychnine, which were not available in our case, may be helpful particularly in the milder phenotypes of the disorder.