ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02525.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractThe use of specific dietary restrictions, cofactor administration, mobilisation of insoluble substances, environmental modifications, product replacement and selective enzyme inhibition are now established for the treatment of some inborn errors of metabolism. There is no generally accepted application for enzyme administration, cytopharmacology (manipulation of the cytoskeleton) or for cell transplantation except for bone marrow transplantation in disorders where the bone marrow is primarily at fault. The other uses of bone marrow transplantation which have been proposed require further evaluation. Results of recent research suggest that the scope of this approach is gradually being widened. There is also scope for development in the field of organ transplantation taking advantage of recent technical1and immunological progress. The treatment of inborn errors of metabolism by genetic modification is not yet on a practical clinical level; more laboratory and animal studies are needed before this can be attempted in man. Adenosine deaminase deficiency appears to be the disease in which this will be first attempted using a retroviral vector to insert the gene into the genome of pluripotential bone marrow cells.

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02526.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractNeurological symptoms in 6‐pyruvoyltetrahydropterin synthase (PTPS) deficiency (formerly called dihydrobiopterin synthetase deficiency) are caused by lack of neurotransmitters in turn due to deficiency of tetrahydrobiopterin (BH4) in the brain. The response to treatment in three patients with PTPS deficiency was variable. Trial of BH4monotherapy in two patients, after three months and one year, respectively, was unsuccessful. We believe that BH4monotherapy is unsafe even in the absence of symptoms. The levels of pterins and neurotransmitter metabolites, and the Ne/B ratio, in the cerebrospinal fluid are more reliable indicators of disease activity than in urine and serum. The prognoses of some patients with PTPS deficiency are poor, and brain damage may developin utero. BH4is transported from mother to fetus in guinea pigs when a large amount of BH4is administered. If this is true in humans, prenatal treatment of PTPS deficiency might be feasibl

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02527.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractThe differential diagnosis of phenylalanine hydroxylase deficiency (PAHD) by biochemical methods is difficult. Using standardized oral protein loading or the intravenous deuterated phenylalanine (phe) load in 46 patients with PAHD, three groups could be distinguished: 1) Phenylketonuria (PKU) with plasma phe levels over 20 mg% under the protein load and with residual activities of less than 1% of normal; 2) mild PKU with plasma phe of 10–20 mg% and residual enzyme activities of 1–3%; 3) Non‐PKU hyperphenylalaninemia with plasma phe levels of less than 10 mg% and residual enzyme activities of more than 3%. Psychomotor development in 32 untreated patients with PAHD showed that there is a high risk of brain damage for all patients within vivoresidual activities of less than 3% of normal. Restriction fragment length polymorphism (RFLP) haplotypes at the phenylalanine hydroxylase (PAH) locus in 60 German patients with PAHD showed that 90% of the mutant alleles are confined to four distinct haplotypes. Using an oligonucleotide probe for the splicing mutation associated with mutant haplotype 3 a close association between the mutation and the haplotype 3 has been observed. There is also an association between haplotypes 2 and 3 and PKU patients with residual enzyme activities of less than 1%. However, in only 37% of our patients with PAHD could a direct diagnosis of the mutations in the PAH gene be made. More knowledge of other mutations in the PAH gene is necessary to differentiate patients with PAHD on the DNA

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02528.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractA method of preparation of low phenylalanine (Phe) peptide fomiula for phenyketonuria (PKU) and the long term therapeutic effects of the milk in 6 PKU infants and one adult female patient aged 24 who wanted to become pregnant, are described. Low phenylalanine peptides (LPP) were prepared from whey protein. After hydrolysis by pronase (actinase), the hydrdysate was passed through a charcoal column to remove aromatic amino acids, and the free amino acids and salts were removed by passing through RD membranes to obtain LPP. Together with vegetable oils, lactose, dextrin, vitamins and minerals, as well as a small amount of amino acid mixture, low phenylalanine milk was madexs by freeze‐drying UP. The product (LPP milk), which does not have the bad taste and odor peculiar to amino acids, was administered to seven patients with PKU for one to three years. There were no differences between the LPP formula and conventional formulae collsisting of amino acids formula (AA formula), in reducing serum Phe levels in PKU patients. There were no adverse effects in patients who received LPP formula. UP formula can be used not only as milk, but also as an ingredient to make more palatable foods of low Phe conten

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02529.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractOur experience to date with 40 pregnancies in 13 women with hyperphenylalaninemia indicates that to prevent mental retardation in their children, maternal phenylalanine levels of 120–600 umol/L are needed, in addition to a newborn screening program. While treatment results to date are preliminary, it appears that the phenylalanine‐restricted diet is of value and should be instituted as soon as pregnancy is planned by phenylketonuric women. There is much to be learned by study of these women and referral to a collaborating center in the National Maternal PKU Collaborative Study is recommen

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02530.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractTreatment results in maple Syrup urine disease can be good if therapy is started before 10 days of age, if there is meticulous control of the plasma branched chain amino acid levels and if relapses are treated immediately.

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02531.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractWe diagnosed 21 patients with hereditary tyrosinemia in Norway; 14 of them had the diagnosis confirmed by enzyme studies. Five died in infancy before dietary treatment was introduced. Six developed hepatoma, between the ages of 3 ½‐ 20 years, three of them while on dietary treatment. Three died from causes other than hepatoma. Of the seven still alive at the time of writing, two received liver transplants, and one a kidney transplant, three are receiving dietary treatment and one is being managed without a special diet.Dietary treatment may be life‐saving in acute cases. It improves the general condition in the chronic forms, improves tubular dysfunction and growth and may postpone develop ment of hepatoma. Liver transplantation is the only curative treatment, but difficulty remains in deciding the optimum time for transplantation; it should ideally be performed before hepatoma deve

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02532.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractA follow‐up study of the cases detected by a newborn mass‐screening program has been performed during 1977–1985 by a collaborative study group.The number of hyperphenylalaninemic patients detected was 148, yielding a calculated incidence of one in 82,000. Of these patients, 102 cases were confired as classical PKU, 37 cases as hyperphenylalaninemia, and 9 cases as biopterine deficiency. The ratio of biopterine deficiency to PKU was about 9%. The incidence of maple syrup urine disease was estimated as one in 580,000, and the incidence of homocystimuria and galactosemia was found to be markedly low. Our survey has accumulated 1,362 cases of histidinemia establishing an incidence of one in 9,000. We have evaluated a large‐scale base to study the cad relation of histidinemia to mental development. It seems that low DQ or IQ scores of some histidinemic patients do not correspond to the blood histidin

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02533.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

AbstractChildren with congenital urea cycle disorders are at a high risk for cerebral damage, mental retardation and other developmental disabilities. Intellectual outcome appears to be correlated with the severity of the underlying cerebral damage and the duration of hyperammonemic coma. Thus, if a good outcome is to Le possible, early diagnosis and treatment is essential. However, even prospective treatment of affected children may not prevent cognitive impairment and even asymptomatic hyperammonemia may have subtle effects on intellect.

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1988.tb02534.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY