Progress in Phenylketonuria: Defects in the Metabolism of Biopterin

PEDIATRICS ◽  
1980 ◽  
Vol 65 (4) ◽  
pp. 837-839
Author(s):  
Stanley Berlow
Keyword(s):  
Early Diagnosis ◽  
Liver Biopsy ◽  
Neurological Disease ◽  
Phenylalanine Hydroxylase ◽  
Clinical Course ◽  
Careful Study ◽  
High Tolerance ◽  
Hydroxylase Activity ◽  
Potential Significance ◽  
New Form

Although progress in a major biological frontier, the neurosciences, has been both rapid and broadly based, it has offered little to the practical pediatrician. Some recent reports may forecast a change. Careful study of an old subject, phenylketonuria (PKU), has opened up a new area of research that has great potential significance. Five years ago in London, Smith et al1 described three children with "PKU" who had an unusual clinical course. Despite early diagnosis and treatment with a low phenylalanine diet, these patients developed progressive neurological disease and died. The atypical course, a high tolerance for phenylalanine, and normal phenylalanine hydroxylase activity on liver biopsy in one of the children led them to the astute speculation that this syndrome was a new form of "hyperphenylalaninemia" probably due to a defect in the metabolism of biopterin.

scholarly journals A tetrahidrobiopterin (BH4)-deficientia diagnosztikája és kezelése

2017 ◽  
Vol 158 (48) ◽  
pp. 1897-1902 ◽  
Author(s):  
János Bókay
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Retardation ◽  
Phenylalanine Hydroxylase ◽  
Clinical Course ◽  
Hydroxylase Activity ◽  
Mild Form ◽  
Tetrahydrobiopterin Deficiency ◽  
The Central Nervous System ◽  
Phenylalanine Metabolism

Abstract: Since the initial breaking discovery of Følling that the severe neurological consequences of phenylketonuria could be prevented by use of low phenylalanine (Phe) diet, it has been shortly recognised that defective phenylalanine metabolism may also arise from the deficiency of tetrahydrobiopterin (BH4) cofactor, required for phenylalanine-hydroxylase activity. Furthermore, as BH4 is in Phe metabolism, it is also a cofactor for the activities of tyrosine hydroxylase and tryptophane hydroxylase, enzymes required for the synthesis of catecholamines and serotonin neurotransmitters. Besides hyperphenylalaninemia in patients with tetrahydrobiopterin deficiencies, dopamine and serotonin deficiencies, with different disorders of the central nervous system also develop. Mild form of tetrahydrobiopterin deficiency is rare, most of the patients have severe neurological abnormalities including progressive mental retardation if not treated properly. Early diagnosis and treatment are essential and can improve the clinical course and prognosis. Orv Hetil. 2017; 158(48): 1897–1902.

A Case of Hemobilia Secondary to Percutaneous Liver Biopsy: The Clinical Course of Spontaneous Recovery and Changes of "Color Mosaic Appearance" on Color Doppler Sonogram

Choonpa Igaku ◽  
2006 ◽  
Vol 33 (6) ◽  
pp. 673-679
Author(s):  
Shuichi YAMAMOTO ◽  
Hitoshi MARUYAMA ◽  
Ayaka SEZA ◽  
Yoshio MASUYA ◽  
Toshio TUYUGUCHI ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Spontaneous Recovery ◽  
Clinical Course ◽  
Color Doppler ◽  
Percutaneous Liver Biopsy

Development of phenylalanine hydroxylase activity in guinea pig liver

1972 ◽  
Vol 261 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Helen K. Berry ◽  
Roberta Cripps ◽  
Kay Nicholls ◽  
David McCandless ◽  
Calvin Harper
Keyword(s):  
Guinea Pig ◽  
Phenylalanine Hydroxylase ◽  
Hydroxylase Activity ◽  
Pig Liver ◽  
Guinea Pig Liver

Clinical and Genetic Characteristics of Phenylketonuria in Ryazan Region

2021 ◽  
Vol 29 (1) ◽  
pp. 5-12
Author(s):  
Grigorii I. Yakubovskii ◽  
Olga B. Serebriakova ◽  
Alina G. Yakubovskaya ◽  
Nadezhda V. Ruban ◽  
Angelina A. Lyakhovets
Keyword(s):  
Blood Level ◽  
Phenylalanine Hydroxylase ◽  
Clinical Course ◽  
Molecular Genetic ◽  
Residual Activity ◽  
Speech Development ◽  
Genetic Characteristics ◽  
Frequent Mutations ◽  
R408w Mutation ◽  
Pah Gene

Aim. This investigation seeks to determine the incidence of phenylketonuria in the Ryazan region, assess the spectrum of mutations in the PAH gene (phenylalanine hydroxylase), investigate the interrelationship between the diseases clinical course, the phenylalanine blood level, and the patients genotype. Materials and Methods. The incidence of phenylketonuria was studied based on the data of massive neonatal screening for the period from 2000 to 2019. Molecular genetic examination of mutations was conducted in 39 patients using the allele-specific multiplex ligation method. The interrelationship between the phenylalanine blood level on the fifth day of life and retest, the diseases clinical course, and the patients genotype was assessed according to the medical record data of 33 patients under dispensary observation in a medico-genetic clinic. The patients were divided into two groups. The first group (n=21) had two severe mutations (residual activity of phenylalanine hydroxylase 10%). The second group (n=12) had one severe and one mild mutation (the residual activity of the enzyme 10%). Results. The incidence of phenylketonuria in the Ryazan region was one in 5054 newborns, exceeding the Russian Federations average parameters. Eighteen mutations were discovered in the PAH gene. The most frequent was the R408W mutation (56.4% alleles). The second most frequent mutations were the IVS10-11GA (6.4%) and P281L (5.1%). The R158Q and Y418C mutations occurred with a frequency of 4.1% and Е280К mutation of 2.7%. All the rest of the mutations occurred as single cases. Investigation of the interrelationship between the phenylalanine blood level, the diseases clinical course, and the patients genotype revealed a reliably higher content of amino acid in the first group on retest (32.11.7 mg/% vs. 17.71.5 mg/% in the second group, р0.001) and predomination of more severe forms of phenylketonuria (90.5% vs. 41.7%, respectively, р0.001). Disorders in neuropsychic and speech development were present in 28.6% of patients in the first group but were absent in the second group. Conclusion. By conducting the study, the incidence of phenylketonuria was determined in the Ryazan region. The spectrum of mutations in the PAH gene was defined. The interrelationship between the diseases clinical portrait, the phenylalanine blood level, and the patients PAH genotype was revealed.

HEARING LOSS IN RETINITIS PIGMENTOSA

PEDIATRICS ◽  
1967 ◽  
Vol 40 (5) ◽  
pp. 875-880
Author(s):  
Richard L. Goode ◽  
F. Mark Rafaty ◽  
F. Blair Simmons
Keyword(s):  
Hearing Loss ◽  
Early Diagnosis ◽  
Retinitis Pigmentosa ◽  
Clinical Course ◽  
Family Members ◽  
Onset Age ◽  
Hearing Tests ◽  
Historical Information ◽  
Hearing Defect ◽  
Visual Abnormalities

The clinical course of hearing loss associated with retinitis pigmentosa is outlined in four brief case summaries. This incidence of hearing loss in retinitis pigmentosa is 10% and occurs several years before clinical visual abnormalities. A battery of audiometric tests all suggest that the hearing defect is within the cochlea and that it is not rapidly progressive. Onset age has not been established. The employment of more than routine hearing tests, testing of other family members, electroretinograms, and historical information about certain features of familial vision are useful in establishing early diagnosis.

Comparison of Different Methods for the Determination of Phenylalanine Hydroxylase Activity in Rat Liver and Euglena gracilis

1984 ◽  
Vol 39 (7-8) ◽  
pp. 728-733 ◽  
Author(s):  
Rita M. Fink ◽  
Erich F. Elstner
Keyword(s):  
Rat Liver ◽  
Euglena Gracilis ◽  
Phenylalanine Hydroxylase ◽  
Hplc Method ◽  
Enzymic Activity ◽  
Hydroxylase Activity ◽  
Product Separation ◽  
Tyrosine Concentration ◽  
Layer Chromatography

Abstract Three different methods for the determination of phenylalanine hydroxylase activity have been compared: a) Differential photometric assay of the increase in tyrosine concentration in the presence of phenylalanine; b) Product separation by thin layer chromatography and scintillation counting of the [14C]tyrosine formed;c) HPLC separation and spectrofluorometric quantification of derivatized amino acids. A comparison of the activities of phenylalanine hydroxylase in rat liver and Euglena gracilis clearly showed that only rat liver contains this enzymic activity as shown by methods b) and c) although pseudo-activity of Euglena gracilis preparations was found during the spectrophotometric test a). The HPLC method proved to be the fastest, most reliable and convenient method for direct tyrosine determination and thus for measuring phenylalanine hydroxylase activity.

scholarly journals Molecular-genetic and phenotypic characteristics of desmoid-type fibromatosis

2019 ◽  
pp. 9-15
Author(s):  
T.A. Muzaffarova ◽  
O.V. Novikova ◽  
I.Yu. Sachkov ◽  
F.M. Kipkeeva ◽  
E.K. Ginter ◽  
...  
Keyword(s):  
Clinical Course ◽  
Age Of Onset ◽  
Molecular Genetic ◽  
Germline Mutations ◽  
Apc Gene ◽  
Phenotypic Characteristics ◽  
Potential Significance ◽  
Desmoid Fibromatosis ◽  
Apc Mutations ◽  
Sporadic Tumors

Desmoid-type fibromatosis (DF) is a rare mesenchymal tumor occurring in only 2 to 4 people per 1,000,000 population a year. Desmoid tumors are either seen sporadically or in individuals with familial adenomatous polyposis (FAP). The etiology of sporadic DF is uncertain. The aim of this study was to estimate the potential significance of germline mutations in the APC gene in patients with sporadic DF. APC exons were amplified, studied using conformation sensitive gel electrophoresis and then Sanger-sequenced. The obtained data were processed in Statistica 10. Mutations were detected in 6 (12%) of 51 participants with sporadic DF. Those 6 patients shared a typical DF phenotype characterized by early age of onset (5.8 years on average, in contrast to the patients without APC mutations, who developed DF at 19 years of age; p = 0.02), severe clinical course, multifocal localization on the trunk, and poor prognosis. All of the detected APC mutations were localized to the 3'-end of the gene. For the purpose of comparison, we analyzed a sample of 12 patients with FAP-associated DF. Of those patients, 6 carried mutations in the APC gene. In the analyzed sample, the patients with FAP and the mutant APC gene developed DF at older age (35 years) than the patients with sporadic DF (p = 0.004) and their tumors were not multifocal. This means that sporadic and FAP-associated desmoids have different phenotypes in patients with APC mutations. Patients with sporadic tumors have mutations at the 3'-end of the APC gene more often than individuals with FAP-associated DF. To our knowledge, this is the first study to characterize the subtype of sporadic desmoid fibromatosis phenotypically determined by germline mutations in the APC gene.

scholarly journals Metabolism of phenylalanine in mice homozygous for the gene ‘dilute lethal’

1970 ◽  
Vol 119 (5) ◽  
pp. 895-903 ◽  
Author(s):  
L. I. Woolf ◽  
A. Jakubovic ◽  
F. Woolf ◽  
P. Bory
Keyword(s):  
Natural History ◽  
Phenylalanine Hydroxylase ◽  
Disease Process ◽  
Particulate Fraction ◽  
Hydroxylase Activity ◽  
Phenylpyruvic Acid ◽  
History Of

Mice homozygous for dl have been suggested as models for phenylketonuria. We found: (1) the concentration of phenylalanine in the blood was normal at all ages examined; (2) phenylalanine hydroxylase activity in the liver in vitro equalled that in unaffected littermates; (3) the apparent Km values for phenylalanine and cofactor respectively in dl/dl mice were the same as in their normal littermates; (4) inhibition of the overall reaction by the particulate fraction, excess of substrate, excess of cofactor or phenylpyruvic acid showed no difference between dl/dl mice and their unaffected littermates; (5) phenylalanine injected in vivo had equal, small, effects on phenylalanine hydroxylase activity of the liver measured in vitro in the two groups of mice. An explanation of the findings of other workers, based on the natural history of the disease process, is tentatively put forward.

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