Journal of Neurology

, Volume 261, Issue 12, pp 2446–2448 | Cite as

Adult-onset phenylketonuria revealed by acute reversible dementia, prosopagnosia and parkinsonism

  • Francesca Rosini
  • Alessandra Rufa
  • Lucia Monti
  • Letizia Tirelli
  • Antonio FedericoEmail author
Letter to the Editors

Dear Sirs,

Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficiency of phenylalanine hydroxylase (PAH) enzyme [1], usually manifesting in infancy; however, rare cases of adult onset of PKU symptoms have been described [2, 3, 4, 5, 6].

A 46-year-old female, with mild learning difficulties (middle-school degree achieved), was observed for rapidly progressive dementia, walking difficulties and visual impairment started 1 month before, at the end of 6-month unbalanced diet for slimming. Her older sister, presenting with fair hair and skin (similarly to their unaffected mother), mental retardation and spastic tetraparesis, was diagnosed with PKU in infancy. Patient’s newborn screening was reported as negative. Her physical examination disclosed fair hair with blue eyes. Neurologic examination showed inability to walk, aphasia, prosopagnosia, extrapyramidal signs and brisk tendon reflexes. Fundoscopy revealed pale optic disks. Brain MRI evidenced diffuse bihemispheric...


Newborn Screening Phenylketonuria White Matter Abnormality Unbalanced Diet Prosopagnosia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research has been in part supported by a grant from Regione Toscana and National Ministry of Health to AF. Authors kindly thank Dr. F. Calì, Laboratorio di Genetica Molecolare, U.O.C. di Genetica Medica, Associazione OASI Maria SS. ONLUS—IRCCS, Troina, EN, for the execution of the genetic testing.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

Patient’s anonymity was protected in this case report.


  1. 1.
    Weglage J, Möller HE, Wiedermann C, Cipcic-Schmidt S, Zschocke J, Ullrich K (1998) In vivo NMR spectroscopy in patients with phenylketonuria: clinical significance of interindividual differences in brain phenylalanine concentrations. J Inherit Metab Disord 21:81–82CrossRefGoogle Scholar
  2. 2.
    Kasim S, Moo R, Zschocke J, Jinnah HA (2001) Phenylketonuria presenting in adulthood with progressive spastic paraparesis and dementia. J Neurol Neurosurg Psichiatry 71:795–797CrossRefGoogle Scholar
  3. 3.
    Weglage J, Oberwittler C, Marquardt T, Schellscheidt J, von Teeffelen-Heithoff A, Koch G, Gerding H (2000) Neurological deterioration in adult phenylketonuria. J Inherit Metab Dis 23:83–84CrossRefPubMedGoogle Scholar
  4. 4.
    Ishimaru K, Tamasawa N, Baba M, Matsunaga M, Takebe K (1993) Phenylketonuria with adult-onset neurological manifestation. Rinsho Shinkeigaku 33:961–965PubMedGoogle Scholar
  5. 5.
    Jousserand G, Antoine JC, Camdessanché JP (2010) Musty odour, mental retardation, and spastic paraplegia revealing phenylketonuria in adulthood. J Neurol 257:302–304CrossRefPubMedGoogle Scholar
  6. 6.
    Narayanan D, Barski R, Henderson MJ, Luvai A, Chandrajay D, Stainforth C, Bradley J, Rogozinski H, Sharma R (2014) Delayed diagnosis of phenylketonuria—a case report of two siblings. Ann Clin Biochem 51:406–408CrossRefPubMedGoogle Scholar
  7. 7.
    Anderson PJ, Leuzzi V (2010) White matter pathology in phenylketonuria. Mol Genet Metab 99:S3–S9CrossRefPubMedGoogle Scholar
  8. 8.
    Cleary MA, Walter JH, Wraith JE, White F, Tyler K, Jenkins JP (1995) Magnetic resonance imaging in phenylketonuria: reversal of cerebral white matter change. J Pediatr 127:251–255CrossRefPubMedGoogle Scholar
  9. 9.
    Pietz J, Kreis R, Schmidt H, Meyding-Lamadé UK, Rupp A, Boesch C (1996) Phenylketonuria: findings at MR imaging and localized in vivo H-1 MR spectroscopy of the brain in patients with early treatment. Radiology 201:413–420CrossRefPubMedGoogle Scholar
  10. 10.
    Oka M, Hasegawa S, Matsushige T, Inoue H, Kajimoto M, Ishikawa N, Isumi H, Ichiyama T (2014) Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis. Brain Dev 36:16–20CrossRefPubMedGoogle Scholar
  11. 11.
    Weglage J, Wiedermann D, Denecke J, Feldmann R, Koch HG, Ullrich K, Moller HE (2002) Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria. J Inherit Metab Dis 25:431–436CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Francesca Rosini
    • 1
  • Alessandra Rufa
    • 1
  • Lucia Monti
    • 2
  • Letizia Tirelli
    • 1
  • Antonio Federico
    • 1
    Email author
  1. 1.Department of Medical, Surgical and Neurological Sciences, Medical SchoolUniversity of Siena, Policlinico Santa Maria Alle ScotteSienaItaly
  2. 2.Unit NINT Neuroimaging and NeurointerventionAOU Senese, Policlinico Santa Maria Alle ScotteSienaItaly

Personalised recommendations