No abstract available.
Phenylketonurias*

No abstract available.
Phenylketonurias*

In this untreated classic phenylketonuria (PKU) case, mental retardation is severe; however, there have been individuals-like the mother of this case who have escaped mental retardation and all the other potential sequelae of phenylketonuria, despite having high blood phenylalanine levels, and very poor dietary control. It appears that they have nearly normal brain phenylalanine levels despite high blood phenylalanine (Phe) levels. A number of studies have now demonstrated considerable variability in blood vs. brain phenylalanine levels in phenylketonuria patients. Outcome of phenylketonuria appears to be related to brain phenylalanine levels. We report a case of "undiagnosed" maternal phenylketonuria syndrome. A female infant had low birth weight (2,400 g) with microcephaly. We examined her family and discovered that her mother was an undiagnosed phenylketonuria patient with a borderline intelligence quotient (IQ). The infant's sister, six years old, was diagnosed with phenylketonuria at the age of four years was mentally retarded and had received an operation for cleft lip and palate. the sister had also had a low birth weight (2,300 g). Her sister and mother were compound heterozygotes (mother: R243Q/Y325X; sister: Y325X/P407S). The infant and father were heterozygous carriers (baby: R243Q/-; father: P407S/-).
Brain ; Cleft Lip ; Fathers ; Female ; Heterozygote ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Intellectual Disability ; Intelligence ; Mentally Disabled Persons ; Microcephaly ; Mothers ; Palate ; Parturition ; Phenylalanine ; Phenylalanine Hydroxylase ; Phenylketonuria, Maternal ; Phenylketonurias ; Siblings ; United Nations

OBJECTIVETo establish a hyperphenylalaninemia related genes screening method using Ion Torrent Personal Genome Machine (PGM) for early detection and differential diagnosis of hyperphenylalaninemia (HPA).

METHODSThree children with known HPA mutations and a healthy control were used for setting up the method. Ten children with HPA with known mutations were recruited for validating the method. Ion Ampliseq PCR was used to amplify the 5' and 3' untranslated region, coding sequence, and flanking introns of PAH, GCH1, PTS, QDPR, and PCBD1 genes. After the enrichment with the Ion OneTouch system, the products were sequenced by PGM. Data from the PGM were processed with Torrent Suite v2.2 software package. All variations were confirmed by Sanger sequencing.

RESULTSFor the 4 samples, the PGM output was 94.22 Mb, with approximately 99.5% of reads mapping to the target regions. Among these samples, we detected 74 variations (28 positions) including 6 known mutations. Compared with database and results of Sanger sequencing, 55 (18 positions) polymorphisms and 13 (4 positions) false positive calls were confirmed. For the 10 samples, all the known mutations were successfully identified.

CONCLUSIONIon Torrent PGM sequencing is suitable for screening genetic mutation underlying HPA from the perspective of metabolic pathways, which can meet the clinical demand for individualized diagnosis and treatment.

High-Throughput Nucleotide Sequencing ; methods ; Humans ; Mutation ; Phenylketonurias ; genetics

OBJECTIVETo investigate the type and frequency of mutations in exon 7 of phenylalanine hydroxylase (PAH) gene among children with phenylketonuria (PKU) in Ningxia, China and to provide a basis for the genetic diagnosis and prenatal diagnosis of PKU in this region.

METHODSDirect sequencing of PCR product was performed to analyze the sequences of exon 7 and its flanking introns of 146 PAH alleles in 73 children with typical PKU (39 cases of Hui nationality and 34 cases of Han nationality) in Ningxia.

RESULTSSix mutations were detected, including R243Q (14.4%), R241C (6.8%), IVS7+2T→A (2.7%), L255S (0.7%), G247V (0.7%), and G247R (0.7%). The overall frequency of mutations (missense mutation and splice site mutation) in exon 7 was 26.0% (38/146). The detection rate of R241C mutation was significantly higher in children of Hui nationality than in children of Han nationality(10% vs 3%; P<0.05).

CONCLUSIONSIn Ningxia, R243Q mutation in exon 7 of PAH gene is most common in children with PKU, followed by R241C. The frequency of R241C mutation in exon 7 of PAH gene varies between children with PKU of Hui and Han nationality.

China ; ethnology ; Exons ; Humans ; Mutation ; Phenylalanine Hydroxylase ; genetics ; Phenylketonurias ; genetics

The Guthrie bacterial inhibition assay (BIA) tests for elevated phenylalanine (PHE) by measuring B. subtilis growth zone density in an agar medium. Dried blood spots with elevated PHE on initial BIA screening undergo repeat BIA testing and thin-layer chromatography (TLC). Specimens with elevated PHE by TLC or BIA on second-tier testing require recall. To streamline PKU screening and reduce the recall rate, we tested a modified BIA protocol incorporating autoclaving of dried blood spots. Autoclaving improves growth zone appearance and has been previously reported to reduce the number of specimen requiring repeat testing. From June to October 2006, dried blood spot samples with initially elevated PHE were autoclaved at 110°C for 5 min, then retested by BIA. Samples with still-elevated PHE were analyzed by TLC. 1078 of 37,268 samples (2.89%) had initially elevated PHE. After autoclaving, 1036 no longer exhibited elevated PHE decreasing to 42 (0.11%) the number requiring TLC. By comparison, the unmodified algorithm resulted in 3.14% of samples received from July - December 2006 requiring both repeat BIA and TLC testing. We have since modified our PKU screening algorithm to require repeat BIA testing from autoclaved samples prior to TLC analysis. This translates to a significant reduction in time and resources for second-tier testing and follow-up, and prevents stress for the parents of a newborn who would have been recalled unnecessarily.

Agar ; Chromatography, Thin Layer ; Phenylalanine ; Mandatory Testing ; Parents ; Algorithms ; Phenylketonurias

Animals ; Biopterin ; analogs & derivatives ; therapeutic use ; Genetic Therapy ; Humans ; Phenylalanine Ammonia-Lyase ; administration & dosage ; Phenylketonurias ; therapy

OBJECTIVEThe retrospective study was carried out to investigate the nation-wide neonatal screening program in the past 22 years in China. This study aimed to summarize the experience, analyze the questions and concerns in the screening program.

METHODSAll data on the national neonatal screening in the past 22 years were from National Center for Clinical Laboratory. Study items included the development and mode of the program, screening method adopted as well as the clinical records of prevalence, treatment and follow-up etc.

RESULTSNeonatal screening has become universal since 1985 in China. There were three modes of screening and treatment. From 1985 to 2006, a total of 13,229,242 newborns were screened for congenital hypothyroidism (CH) and 6505 were diagnosed as CH at a prevalence of 49.2/100,000; a total of 13,666,750 newborns were screened for phenylketonuria (PKU), and 1,170 were diagnosed as PKU at a prevalence of 8.6/100,000. The prevalence of CH increased year by year and the western regions in China had a much higher prevalence. The prevalence of PKU was relatively more steady than that of CH in China.

CONCLUSIONSNeonatal screening is of paramount importance in preventing mental retardation and developmental delay after CH and PKU. It is necessary to attach more importance to increase the rate of coverage, screening and treatment, as well as social awareness of neonatal screening. It is important to focus on establishment of new screening techniques so as to improve the level of child health care in China.

China ; epidemiology ; Congenital Hypothyroidism ; epidemiology ; Humans ; Infant, Newborn ; Neonatal Screening ; Phenylketonurias ; epidemiology ; Prevalence ; Retrospective Studies

China ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; diagnosis ; therapy ; Neonatal Screening ; Phenylketonurias ; diagnosis ; Tandem Mass Spectrometry

OBJECTIVETo investigate the factors influencing the quality of life (QOL) of children with phenylketonuria (PKU) in Anhui Province, China.

METHODSA total of 104 PKU children who were diagnosed and treated in three major maternal and child health hospitals in Anhui Province were enrolled as study subjects. The PedsQL™ 4.0 Generic Core Scales were used to evaluate the quality of life of these children. The multivariate logistic regression analysis was used to evaluate the factors influencing the QOL.

RESULTSThe 104 PKU children had significantly lower overall QOL score and scores on the subscales of physiological functioning, emotional functioning, and social functioning than the general school-age children (P<0.01). They also had a significantly lower score on the physiological domain consisting of emotional functioning, social functioning, and role functioning than the general school-age children (P<0.01). The multivariate logistic regression analysis showed that an older age (≥4 years) of PKU children was the risk factor for poor QOL (OR=8.569, P<0.01), and guardians' engagement at enterprises or institutions was the protective factor for QOL (OR=0.206, P<0.05).

CONCLUSIONSPKU children have a low level of QOL, and age and guardians' occupation are factors influencing the QOL.

Adolescent ; Age Factors ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Logistic Models ; Male ; Phenylketonurias ; psychology ; Quality of Life