Læknablaðið - 15.06.2011, Síða 12

RANNSÓKN
Meðferðarmöguleikar PKU hafa aukist undanfarin ár. Auðvelt
er að fá nokkuð fjölbreytt Phe-snautt fæði. í dag taka nokkrir
íslendingar með PKU stórar hlutlausar amínósýrur og geta þar
af leiðandi gefið aðeins eftir í hefðbundinni meðferð. Við BH4-
gjöf öðlast einstaklingarnir mikið frelsi sem öðrum finnst annars
sjálfgefið eins og að borða úr öllum fæðuflokkum, þurfa ekki að
hafa hugann við hvað borðað er öllum stundum eða taka inn mikið
magn af töflum og blöndum. Einnig verða síðkomnir fylgikvillar
PKU ólíklegri, sérstaklega ef BH4-meðferð er beitt fyrstu æviárin.10
Samkvæmt töflu TII svöruðu tveir arfblendnir Y377fsdelT-berar
ekki BH4-hleðsluprófi. Þeir bera báðir P281L á hinni samsætunni
en vitað er að P281L svarar BH4-hleðsluprófi ekki.23 Niðurstaða
okkar sýnir að íslenska stökkbreytingin Y377fsdelT svarar ekki
BH4-meðferð. BH4-svörun Y414C var áður þekkt.12 Tveir úr þýði
okkar með Y414C svara BH4-meðferð (tafla III). Fjórir til viðbótar
bera stökkbreytingar sem þekktar eru af því að svara BH4-
hleðsluprófi, þrír með R68S og einn með A403V.12'23 Áhugavert
væri að sjá hvort þeir svari BH4-hleðsluprófi og geti því hafið
BH4-meðferð.
Ungt fólk sem glímir í dag við PKU á oft í miklum erfiðleikum
með að stjórna meðferð sirrni á fullnægjandi hátt þrátt fyrir hjálp
foreldra og aðstandenda.24 Margir þeir sem eru með PKU á Islandi
eru á unglingsaldri eða að nálgast hann. Huga má að þessum
aldurshópi enn frekar, veita frekari fræðslu og aðstoð til að ná
fullum tökum á meðferðinni.
Þakkir fá þátttakendur og aðstandendur þeirra, Ásgeir Haraldsson
og Jón Jóhannes Jónsson.
Heimiidir
1. Guldberg P, Zschocke J, Dagbjartsson A, Henriksen
KF, Guttler F. A molecular survey of phenylketonuria
in Iceland: identification of a founding mutation and
evidence of predominant Norse settlement. Eur J Hum
Genet 1997; 5:376-81.
2. Erlandsen H, Patch MG, Gamez A, Straub M, Stevens
RC. Structural studies on phenylalanine hydroxylase
and implications toward understanding and treating
phenylketonuria. Pediatrics 2003; 112:1557-65.
3. Bowden JA, McArthur CL, 3rd. Possible biochemical
model for phenylketonuria. Nature 1972; 235: 230.
4. Hanley WB. Adult phenylketonuria. Am J Med 2004; 117:
590-5.
5. Kayaalp E, Treacy E, Waters PJ, Byck S, Nowacki P, Scriver
CR. Human phenylalanine hydroxylase mutations and
hyperphenylalaninemia phenotypes: a metanalysis of
genotype-phenotype correlations. Am J Hum Genet 1997;
61:1309-17.
6. Scriver CR, Sly S, eds. The Metabolic and Molecular Bases
of Inherited Disease. 8.ed. McGraw-Hill Professional, New
York 2000.
7. Antoshechkin AG, Chentsova TV, Tatur V, Naritsin DB,
Railian GP. Content of phenylalanine, tyrosine and their
metabolites in CSF in phenylketonuria. J Inherit Metab Dis
1991; 14: 749-54.
8. Holtzman NA, Welcher DW, Mellits ED. Termination
of restricted diet in children with phenylketonuria: a
randomized controlled study. N Engl J Med 1975; 293:
1121-4.
9. Homer FA, Streamer CW, Clader DE, Hassell LL, Binkley
EL Jr, Dumars KW Jr. Effect of phenylalanine-restricted
diet in phenylketonuria. II. AMA J Dis Child 1957; 93: 615-
8.
10. Abadie V, Berthelot J, Feillet F, et al. [Management of
phenylketonuria and hyperphenylalaninemia: the French
guidelines]. Arch Pediatr 2005; 12: 594-601.
11. National Institutes of Health Consensus Development
Conference Statement: phenylketonuria: screening and
management, October 16-18, 2000. Pediatrics 2001; 108:
972-82.
12. Blau N, Erlandsen H. The metabolic and molecular
bases of tetrahydrobiopterin-responsive phenylalanine
hydroxylase deficiency. Mol Genet Metab 2004; 82:101-11.
13. Bremer HJ, Marx D, Nutzenadel W, Bickel H. [Thin-
layer chromatography of urinary amino acids]. Klin
Wochenschr 1970; 48: 682-8.
14. Bernegger C, Blau N. High frequency of tetrahydrobio-
pterin-responsiveness among hyperphenylaaninemias: a
study of 1,919 patients observed from 1988 to 2002. Mol
Genet Metab 2002; 77: 304-13.
15. O'Neill CA, Eisensmith RC, Croke DT, Naughten ER,
Cahalane SF, Woo SL. Molecular analysis of PKU in
Ireland. Acta Paediatr Suppl 1994; 407:43-4.
16. Ozalp I, Coskun T, Tokatli A, et al. Newbom PKU
screening in Turkey: at present and organization for
future. Turk J Pediatr 2001; 43: 97-101.
17. Dobson JC, Williamson ML, Azen C, Koch R. Intellectual
assessment of 111 four-year-old children with
phenylketonuria. Pediatrics 1977; 60: 822-7.
18. Waisbren SE, Levy HL. Agoraphobia in phenylketonuria. J
Inherit Metab Dis 1991; 14: 755-64.
19. Thompson AJ, Smith I, Brenton D, et al. Neurological
deterioration in young adults with phenylketonuria.
Lancet 1990; 336: 602-5.
20. Stevenson RE, Huntley CC. Congenital malformations in
offspring of phenylketonuric mothers. Pediatrics 1967; 40:
33-45.
21. Eiken HG, Knappskog PM, Boman H, et al. Relative
frequency, heterogeneity and geographic clustering of
PKU mutations in Norway. Eur J Hum Genet 1996; 4: 205-
13.
22. O'Donnell KA, O'Neill C, Tighe O, et al. The mutation
spectrum of hyperphenylalaninaemia in the Republic of
Ireland: the population history of the Irish revisited. Eur J
Hum Genet 2002; 10: 530-8.
23. Bardelli T, Donati MA, Gasperini S, et al. Two novel genetic
lesions and a common BH4-responsive mutation of the
PAH gene in Italian patients with hyperphenylalaninemia.
Mol Genet Metab 2002; 77: 260-6.
24. Weglage J, Fiinders B, Ullrich K, Rupp A, Schmidt E.
Psychosocial aspects in phenylketonuria. Eur J Pediatr
1996; 155 Suppl 1: SlOl-4.
ENGLISH SUMMARY
Phenylketonuria (PKU) in lceland
Oddason KE, Eiriksdottir L, Franzson L, Dagbjartsson A
Introduction: PKU is a metabolic disorder caused by a mutation in the phenylalanine hydroxylase (PAH) gene. Icelandic neonatal screening for
PKU started in 1972. The mutation causes a varible dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor
tetrahydrobiopterin (BH4). Accumuiation of Phe causes mental retardation and seizures. Current therapy focuses on Phe-restrictive diet and newer
methods like BH4 in large doses. The primary aim was to collect data about PKU in lceland and evaluate therapy and screening. Additional focus was on
BH4 therapy.
Materials and methods: Information was gathered from Landspitali medical charts retrospectively. Serum-Phe (S-Phe) measurements, age at initiation of
therapy, PAH mutation types and information on current therapy was collected. Results from BH4 loading tests were collected.
Results: 27 patients have been diagnosed with PKU in lceland since 1947. Incidence 1972-2008 is 1/8400 living births. Classic PKU is the most common
presentation in lceland. Patients diagnosed after screening started have normal intelligence. Age at initiation of therapy and S-Phe average values lower
with time. 12 PAH mutation types have been found in lceland. A novel lcelandic mutation, Y377fsdelT, did not respond to BH4 loading test. Two patients
responded to a BH4 loading test and four other patients are likely to respond to BH4 loading test.
Conclusion: PKU incidence in lceland is slightly higherthan in neighboring countries. Therapy compliance is adequate and international consensuses
regarding therapy are met. PKU patients in lceland are generally in good health. Screening is efficient and save. BH4 therapy is a an optional alternative
therapy in lceland.
Key words: Phenylketonuria (PKU), incidence, screening, therapy, phenyiaianine hydroxylase (PAH), tetrahydrobiopterin (BH4), Serum-Phe (S-Phe).
Correspondence: Atli Dagbjartsson, atlid@landspitali.is
352 LÆKNAblaðið 2011/97