I was wondering if there was any association between phenylketonuria (PKU) and stuttering. I have tried searching the literature, but unfortunately couldn't find much at all (other a paragraph on p58 of Multilingual Aspects of Fluency Disorders by Howell et al). In your opinion, is it possible for PKU (or its various subtypes) to cause a person to stutter? Why or why not? I am mostly interested in the genetic and pharmacological side of things but would really appreciate any input on the topic.
Check out Fragile X Syndrome. I believe PKU and stuttering (and "cluttering") are associated with it.
Ali - Thanks. I've already had a look at that book - specifically the section on stuttering and PKU. It only really mentioned the two in passing and unfortunately, doesn't quite have the info I'm looking for. That said, it seems like a pretty decent book.
Edward - Thanks. I'll check it out.
EDIT: The wikipedia page for Tetrahydrobiopterin states, "The chronic presence of PKU can result in severe brain damage, including symptoms of mental retardation, microcephaly, speech impediments such as stuttering, slurring, and lisps, seizures or convulsions, and behavioral abnormalities, among other effects".
Does anyone have a reference for this?
Perhaps one of these publications related to BH4 can answer your question:
Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Curr Drug Metab. Apr 2002;3(2):123-31. [Medline].
Li H, Förstermann U. Pharmacological Prevention of eNOS Uncoupling. Curr Pharm Des. Oct 29 2013;[Medline].
Dubois M, Delannoy E, Duluc L, et al. Biopterin metabolism and eNOS expression during hypoxic pulmonary hypertension in mice. PLoS One. 2013;8(11):e82594. [Medline]. [Full Text].
Kim HK, Ha SH, Han J. Potential therapeutic applications of tetrahydrobiopterin: from inherited hyperphenylalaninemia to mitochondrial diseases. Ann N Y Acad Sci. Jul 2010;1201:177-82. [Medline].
Crabtree MJ, Hale AB, Channon KM. Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling intetrahydrobiopterin deficiency. Free Radic Biol Med. Jun 1 2011;11:1639-46. [Medline].
Adlam D, Herring N, Douglas G, et al. Regulation of ß-adrenergic control of heart rate by GTP-cyclohydrolase 1 (GCH1) and tetrahydrobiopterin. Cardiovasc Res. Mar 15 2012;93(4):694-701. [Medline]. [Full Text].
Thony B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Hum Mutat. Sep 2006;27(9):870-8. [Medline].
Fiori L, Fiege B, Riva E, Giovannini M. Incidence of BH4-responsiveness in phenylalanine-hydroxylase-deficient Italian patients. Mol Genet Metab. Dec 2005;86 Suppl 1:S67-74. [Medline].
Liu TT, Chiang SH, Wu SJ, Hsiao KJ. Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese. Clin Chim Acta. Nov 2001;313(1-2):157-69. [Medline].
Nalin T, Perry ID, Sitta A, et al. Optimized loading test to evaluate responsiveness to tetrahydrobiopterin (BH4) in Brazilian patients with phenylalanine hydroxylase deficiency. Mol Genet Metab. 2011;104 Suppl:S80-5. [Medline].
Pangkanon S, Charoensiriwatanamsc W, Liamsuwanmd S. 6-pyruvoyltetrahydropterin synthase deficiency two-case report. J Med Assoc Thai. Jun 2006;89(6):872-7. [Medline].
Farrugia R, Scerri CA, Montalto SA, Parascandolo R, Neville BG, Felice AE. Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population. Mol Genet Metab. Mar 2007;90(3):277-83. [Medline].
Ye J, Yang Y, Yu W, Zou H, Jiang J, Yang R, et al. Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: results of a retrospective, multicentre study. J Inherit Metab Dis. Nov 9. 2012;[Medline].
Shintaku H, Ohwada M. Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan. Brain Dev. Jul 23. 2012;[Medline].
Opladen T, Hoffmann GF, Blau N. An international survey of patients with tetrahydrobiopterin deficiencies presenting with hyperphenylalaninaemia. J Inherit Metab Dis. Nov 2012;35:963-73. [Medline].
Feillet F, Chery C, Namour F, et al. Evaluation of neonatal BH4 loading test in neonates screened for hyperphenylalaninemia. Early Hum Dev. Sep 2008;84(9):561-7. [Medline].
Dhondt JL. Lessons from 30 years of selective screening for tetrahydrobiopterin deficiency. J Inherit Metab Dis. May 11 2010;[Medline].
Opladen T, Abu Seda B, Rassi A, Thöny B, Hoffmann GF, Blau N. Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience. J Inherit Metab Dis. Jun 2011;3:819-26. [Medline].
Mikami H, Matsubara Y, Hayasaka K, Narisawa K, Obinata M, Watanabe A, et al. Molecular analysis of dihydropteridine reductase deficiency and restoration of the enzyme activity by gene transfer. J Inherit Metab Dis. 1990;13(5):787-91. [Medline].
Thony B, Leimbacher W, Stuhlmann H, Heizmann CW, Blau N. Retrovirus-mediated gene transfer of 6-pyruvoyl-tetrahydropterin synthase corrects tetrahydrobiopterin deficiency in fibroblasts from hyperphenylalaninemic patients. Hum Gene Ther. Aug 20 1996;7(13):1587-93. [Medline].
Laufs S, Blau N, Thony B. Retrovirus-mediated double transduction of the GTPCH and PTPS genes allows 6-pyruvoyltetrahydropterin synthase-deficient human fibroblasts to synthesize and release tetrahydrobiopterin. J Neurochem. Jul 1998;71(1):33-40. [Medline].
Laufs S, Kim SH, Kim S, Blau N, Thony B. Reconstitution of a metabolic pathway with triple-cistronic IRES-containing retroviral vectors for correction of tetrahydrobiopterin deficiency. J Gene Med. Jan-Feb 2000;2(1):22-31. [Medline].
Tanaka Y, Kato M, Muramatsu T, et al. Early initiation of L-dopa therapy enables stable development of executive function in tetrahydrobiopterin (BH4) deficiency. Dev Med Child Neurol. May 2007;49(5):372-6. [Medline].
Burnett JR. Sapropterin dihydrochloride (Kuvan/phenoptin), an orally active synthetic form of BH4 for the treatment of phenylketonuria. IDrugs. Nov 2007;10(11):805-13. [Medline].
Blau N. The Hyperphenyalaninemias. In: A Differential Diagnosis and International Database of Tetrahydrobiopterin Deficiencies. Tectum Verlag; 1996.
Blau N, Bonafe, Blaskovics ME. Disorders of phenylalanine and tetrahydrobiopterin metabolism. In: Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases. 2nd ed. Berlin, Germany: Springer; 2002:89-106.
Blau N, Erlandsen H. The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Mol Genet Metab. Jun 2004;82(2):101-11. [Medline].
Blau N, Thony B. Tetrahydrobiopterin in biomedical research. J Inherit Metab Dis. Feb 2009;1:1-2. [Medline].
Blau N, Thony B, Cotton RGH. Disorders of tetrahydrobiopterin and related biogenic amines. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B. The Metabolic and Molecular Bases of Inherited Diseases. McGraw-Hill; 2001:1725-76.
Blau N, Thony B, eds. Pterins, Folates, and Neurotransmitters in Molecular Medicine. Heilbronn, Germany: SPS; 2003.
Boveda MD, Couce ML, Castineiras DE, et al. The tetrahydrobiopterin loading test in 36 patients with hyperphenylalaninaemia: evaluation of response and subsequent treatment. J Inherit Metab Dis. Oct 2007;30(5):812. [Medline].
Delgado-Esteban M, Almeida A, Medina JM. Tetrahydrobiopterin deficiency increases neuronal vulnerability to hypoxia. J Neurochem. Sep 2002;82(5):1148-59. [Medline].
Demos MK, Waters PJ, Vallance HD, et al. 6-pyruvoyl-tetrahydropterin synthase deficiency with mild hyperphenylalaninemia. Ann Neurol. Jul 2005;58(1):164-7. [Medline].
Gramer G, Burgard P, Garbade SF, Lindner M. Effects and clinical significance of tetrahydrobiopterin supplementation in phenylalanine hydroxylase-deficient hyperphenylalaninaemia. J Inherit Metab Dis. Aug 2007;30(4):556-62. [Medline].
Jaggi L, Zurfluh MR, Schuler A, et al. Outcome and long-term follow-up of 36 patients with tetrahydrobiopterin deficiency. Mol Genet Metab. Mar 2008;3:295-305. [Medline].
Karacic I, Meili D, Sarnavka V, et al. Genotype-predicted tetrahydrobiopterin (BH4)-responsiveness and molecular genetics in Croatian patients with phenylalanine hydroxylase (PAH) deficiency. Mol Genet Metab. Jul 2009;97(3):165-71. [Medline].
Kaufman S. Tetrahydrobiopterin: Basic Biochemistry and Role in Human Disease. Baltimore, MD: Johns Hopkins University Press; 1997.
Langenbeck U. Classifying tetrahydrobiopterin responsiveness in the hyperphenylalaninaemias. J Inherit Metab Dis. Feb 2008;1:67-72. [Medline].
Longo N. Disorders of biopterin metabolism. J Inherit Metab Dis. Jun 2009;3:333-42. [Medline].
Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L. Dihydropteridine reductase deficiency in man: from biology to treatment. Med Res Rev. Mar 2004;24(2):127-50. [Medline].
Wang CH, Li SH, Weisel RD, et al. Tetrahydrobiopterin deficiency exaggerates intimal hyperplasia after vascular injury. Am J Physiol Regul Integr Comp Physiol. Aug 2005;289(2):R299-304. [Medline].
Wang L, Yu WM, He C, et al. Long-term outcome and neuroradiological findings of 31 patients with 6-pyruvoyltetrahydropterin synthase deficiency. J Inherit Metab Dis. Feb 2006;29(1):127-34. [Medline].
Zurfluh MR, Fiori L, Fiege B, Ozen I, Demirkol M, Gartner KH, et al. Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency. J Inherit Metab Dis. Dec 2006;29(6):725-31. [Medline].
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology