inborn errors of metabolism

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Phenylketonuria 苯丙酮尿症 Xue Fan Gu, MD, PhD Xinhua Hospital Shanghai Jiao Tong University School of Medicine. Inborn errors of metabolism. Overview Disorders in which defects of single gene cause clinically significant blocks in metabolic pathways Many kinds of disorders Lower incidence - PowerPoint PPT Presentation


  • Phenylketonuria

    Xue Fan Gu, MD, PhD Xinhua Hospital Shanghai Jiao Tong University School of Medicine

  • Inborn errors of metabolismOverviewDisorders in which defects of single gene cause clinically significant blocks in metabolic pathwaysMany kinds of disordersLower incidenceClinical manifestations vary widely: mental retardation, seizure, hypotonia, failure to thrive, vomiting/anorexia, special odor, hypoglycemia, hyperammonemia, metabolic acidosis, elevated lactate/pyruvate etc.

  • An autosomal recessive disease

    The incidence of PKU in China is about 1/11 800The incidence of PKU in Shanghai is about 1/16 000


  • Phenylalanine metabolic pathway

    diet protein

    phenylalanine hydroxylase(PAH) phenylalanine tyrosine BH4 phenylpyruvic acid phenyllactate phenylacetate


  • Biosynthesis and regeneration of tetrahydrobiopterin Guanosine triphosphateGTP GTPch p35Neopterin Dihydroneopterin triphosphate (N) PTPS - + 6-Pyruvoyl-tetrahydropterin SR Phe Tyrosine Tryptophan tetrahydropterin(BH4) DHPR PAH TH TPH PCD q-dihydrobiopterin(BH2) pterin- Try L-DOPA 5-OH-Tryptophan 4a-carbinolamine biopterin (B) Dopamine serotonin

  • Clinical manifestationsto appear symptoms after 3 months of birthfair hair, hypopigmentation in skin, eczemaspecial odor (mouse-like) discharged from urine,sweatmental retardationnod-like seizure or infantile spasm

  • Classical PKUPAH activity is about 0-4.4% of normalPersistent elevation of Phe or its metabolites is neurotoxic, the result is profound intellectual handicap Typical PKU symptomsStrong positive result of urinary FeCl3 and DNPH testBlood Phe level is 1200mol/L ( 20mg/dl)

  • Transient PKU Delay in PAH maturityThe Phe level was 1200mol/L at neonatal periodThe Phe level is gradually dropped to normal even on free diet after 2-yearsDietary restriction is only temporary, if required at all

  • Differential diagnosis Tetrahydrobiopterin deficiency BH4DDeficiency of PAH cofactor -- BH4 6-Pyruvoyl-tetrahydropterin synthese (PTPS) deficiency is the most common of BH4DThe incidence of BH4D is 10% among HPA patients in ChineseThe blood Phe is slightly increased at early stage in most patients Some cases were missdiagnosed as having PAH deficiency

  • Neonatal Screening for PKU

    No PKU symptoms in neonatal periodhigher Phe level in blood Neonatal screening program can make diagnosis, treatment earlier and prevent mental retardationNS program has been carried out in China since 1981

  • Neonatal Screening methodSubject Newborns who should be breast-fed for 3 days after birthMethod of Phe determination on Guthrie cardby bacterial inhibition assay (semi-quantity) or fluorescence analysis, the positive cut off of Phe is 120umol/L

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  • Laboratory findings Urine FeCl3 test and DNPH test used in clinical screening for PKU Blood Phe measurement Urinary pterin analysis by HPLCBH4 loading testPAH gene analysis, common PAH gene mutations are in exon 7 in Chinese PKUs

  • TreatmentLow or free Phe milk powder was developed in 1953Low-Phe diet can not only provide proper protein, but also reduce the Phe takingPhe restriction should be continued at least 18 years old or throughout lifeFemale patients must be treated before and whole pregnancy to avoid maternal PKU

  • The series products of low-Phe dietMilk powdercomponent: Protein 15%, Fat 8%,CHO 68%two kinds of: free Phe formula low-Phe formulaFlour,Biscuitpure,aminoacid powder

  • Control range of blood Phe level in different age for treated PKU/HPA AgeY phe levelmol/L _____________________________ 03 120240 38 180360 813 180480 1318 180600 >18 180900 ______________________________

  • Treatment for BH4DTo control Phe concentration
  • PKU patients at the 2 years old untreated patient daignosed by NS and treated

  • M469 4-year old,diagnosed by NS and treated by local-made low-Phe diet


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