MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

nemoci-sympt/METABOLISMUS/fenylketonurie/vysetreni

BH4 responsiveness


Monitorace TYR

  • Blood TYR levels can be low in untreated PKU
  • If TYR is low (less than 0.9 mg/dl)
    • A TYR supplement can be started before making any diet changes
  • TYR supplement of 500 mg twice daily is an appropriate starting dose
  • Absorption can be poor
    • Crushing the tablets before giving them may help
  • Supplementation may need to be continued for some period of time
    • Even though the PKU medical formula product also contains TYR
    • All PKU medical formula products now contain tyrosine in varying amounts
  • In a normal person, 90% of ingested PHE is converted to TYR
  • In PKU, the PHE cannot be converted to TYR
  • Normal level of TYR is approximately 1 mg/dl (55 micromol/L)
    • Supplementation may be necessary when the diet treatment is more intensive.
    • This is especially important during pregnancy.
  • pkunews.org/diet-intervention-guidelines-for-adults-with-untreated-pku/#bioch

Urinary biopterin and neopterin excretion

Neopterin

  • Biosynthetic precusor of tetrahydrobiopterin

Biopterin

  • Appear in urine

Isoxanthopterin in urine

In normal subjects

  • Urinary neopterin to biopterin ratio cca 1.00

Alzheimer's disease, Down's syndrome and depression

  • Urinary neopterin to biopterin ratio has been found to be elevated
  • Some Alzheimer's and depressed patients
    • Increased urinary neopterin to biopterin ratio is proportional to the severity of the disease

47 PKU patients (aged 6 days to 37 years)

  • Affected by age
  • Concomitant blood Phe concentration
  • Influence blood Phe on both biopterin and neopterin levels was greater in patients younger than 4 months
  • Interindividual variability was higher than intraindividual variability for both biopterin and neopterin
  • pubmed.ncbi.nlm.nih.gov/28540433/

48 patients depression before and after placebo, antidepressants, or electroconvulsive therapy (ECT), 26 healthy control s

  • Urinary excretion of neopterins (N) and biopterins (B)
  • Patients prior to and after treatment
    • Significantly greater neopterin/biopterin (N:B) ratio than controls
  • Significant correlation between NB: ratios and severity of depression and plasma cortisol

Raised N:B ratio


Urinary neopterin:biopterin ratios

  • Elevated in senile dementia of the Alzheimer type (SDAT) x age matched controls
    • Reduced conversion of dihydroneopterin triphosphate to tetra-hydrobiopterin
  • Similar elevated neopterin:biopterin ratio in Down's syn-drome - condition producing a similar dementia to SDAT.

Morning urines were collected into ascor-bic acid (2% final concentration) from a group of 53 Downs sufferers 1 to 70 years

  • Neopterin and biopterin levels x group of 35 healthy controls 23 to 93 years
  • Neopterin:biopterin ratio was significantly elevated 3.44, 1.73 vs 1.12, 0.55 (mean, SD) p < 0.2%

Phe and Tyr in heterozygotes for PKU

  • High frequency of heterozygotes in the population (1:50-1:70)

Liver biopsy

  • Activity of PAH enzyme in heterozygotes is about 30%
  • Patients with PKU - PAH acitivity less than 1%

Krevní testy

  • During fasting
  • After oral overload of Phe (25 mg/kg)
  • 23 heterozygotes for PKU (10 men and 13 women) + control group of 27 healthy individuals (13 men and 14 women)
  • Diagnosis of PAH-deficient patients is still a challenge
  • The levels of Phe - highest peak at 30 minutes after overload administration
    • Statistical differences for Tyr levels were detected after 30 min.
  • Largest difference between heteorzygots and controls at 60 min.
  • Tyr in the heterozygote group were 2-fold increased compared to control
  • www.scielo.br/j/jiems/a/MkkMtb9d5dcv67R4mNpGbGD/?lang=en#ModalFigf01

Kolostrum

Zdravé matky

  • Obsah FA v kolostru (prvních 5 dní) činí 70 mg FA/100 ml

Screeningová vyšetření hladiny FA v krvi

  • se provádějí rutinně
  • U PKU přesahuje hladina FA v krvi 480 mcmol/l
  • Poškození mozku dochází při hladině FA vyšší než 900 µmol/l
  • During our 29 year experience with neonatal PKU screening (3.9 million infants tested)-
  • Cutoff blood phenylalanine of 240 mumol/l in blood spots obtained at 24 h of age +
  • Sensitivity of the screening test was 99.2% for infants with classical and mild PKU
  • Ascertainment of patients with MHP is unknown and is very likely incomplete
  • Over a 3-year period (1992-4) the specificity of the test was 99.9% for those screened after 24 h
    • Positive predictive value was 12.8%
    • Early discharge would probably increase the number of infants with MHP missed using the BIA and a cutoff level of 240 mumol/l
  • Recommend that neonates be at least 12 h of age before initial BIA PKU screening be carried out
  • pubmed.ncbi.nlm.nih.gov/9118832/

Urinary metabolites derived from biopterin synthesis and metabolism include

  • D-threo-biopterin
  • L-threo-biopterin (Fukushima and Shiota, 1972)
  • Neopterin,
  • Isoxanthopterin,
  • 7-biopterin (primapterin),
  • N2-(3-aminopropyl)biopterin (oncopterin)
  • Primapterin

Irán screening novorozenců

Novorozenecký screenign v ČR

  • Tandemová hmotnostní spektrometrie (MS/MS) v jedné suché kapce krve
  • 1. října 2009 ve Věstníku Ministerstva zdravotnictví č.6/2009, zavedena do novorozeneckého screeningu PKU a jiných DMP v ČR.
    • Cystické fibrózy (CF)
    • Leucinóza (MSUD)
    • Deficit MCAD,
    • Deficit LCHAD,
    • Deficit VLCAD,
    • Deficit CPT I,
    • Deficit CPT II,
    • Deficit CACT,
    • Glutarová acidurie typ I (GA I)
    • Izovalerová acidurie (IVA)
    • FKU
    • Kongenitální hypotyreóza (CH)
    • Screening vrozeného selhání funkce nadledvin (kongenitální adrenální hyperplazie (CAH)
  • Doba odběru kapky z patičky novorozence na období mezi 48. – 72.h života
  • Ústav dědičných metabolických poruch ve VFN Praha, Olomouc
  • www.nspku.cz/nemoci/screening/screening.html

Přechodové MM

Zdravé ženy

  • 6. až 10. den po porodu - mg/100 ml

Therapeutic range

O úroveň výše

Poslední aktualizace: 18. 12. 2022 2:19:44