Skip to main content
SpringerLink
Log in

Morphologic and histoanatomic observations of the brain in untreated human phenylketonuria

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

The cerebra of three profoundly retarded adult males with untreated phenylketonuria (PKU) were systematically studied in terms of developmental morphology and histoanatomy against normal agematched material, technically comparable in preparation. These studies were made possible by the availability of two extensive reference collections of normative neuroanatomic material, the Yakovlev and the Conel collections. The developmental parameters of myelination, width of the cortical plate, cell packing density, neuronal cell size, development of Nissl granulation, dendritic arborization and synaptic spine populations were studied. Our results indicate that there is a marked curtailment of histoanatomical maturation of the brain in PKU by all developmental parameters studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alvord EC, Stevenson LD, Vogel FS, Engle RL (1950) Neuropathologic findings in phenyl-pyruvic oligophrenia (phenylketonuria). J Neuropathol Exp Neurol 9:298–310

    Google Scholar 

  • Bechar M, Bornstein B, Elian M, Sandbank M (1965) Phenylketonuria presenting an intermittent progressive course. J Neurol Neurosurg Psychiat 28:165–170

    Google Scholar 

  • Bednar B, Jerásek A, Vacek R (1967) Fenylketonurická encefalopatie. Cs Patol 3:221–224

    Google Scholar 

  • Benda CE (1952) Developmental disorders of mentation and cerebral palsy. Grune and Stratton, New York

    Google Scholar 

  • Chase HP, O'Brien D (1970) Effect of excess phenylalanine and of other amino acids on brain development in the infant rat. Pediat Res 4:96–102

    Google Scholar 

  • Clark JTR, Lowden JA (1969) Hyperphenylalanemia: effect on the developing rat brain. Can J Biochem 47:29–295

    Google Scholar 

  • Conel JL (1939–1967). The postnatal development of the human cerebral cortex. Harvard Univ Press, Cambridge

    Google Scholar 

  • Coquet M, Myle G, Nyssen R, Van Bogaert L (1944) Premiere observation verifieé de l'oligophrenie phenylpyruvique. Monatschr Psychiat Neurol 109:135–141

    Google Scholar 

  • Corsellis JAN (1953) The pathological report of a case of phenylpyruvic oligophrenia. J Neurol Neurosurg Psychiat 16:139–143

    Google Scholar 

  • Crome L (1962) The association of phenylketonuria with leukodystrophy. J Neurol Neurosurg Psychiat 25:149–153

    Google Scholar 

  • Crome L, Pare CMB (1960) Phenylketonuria, a review and a report of the pathological findings in four cases. J Ment Sci 106: 862–883

    Google Scholar 

  • Cunningham TJ, Nigam M (1979) Evidence for increased neuron surval in the cerebral cortex of hyperphenylalanemic rats. Anat Rec 193:515

    Google Scholar 

  • Dckaban AS, Sodowsky D (1978) Changes in brain weight during the span of human life. Relation of brain weight to body heights and body weights. Ann Neurol 4:345–356

    Google Scholar 

  • Fellman JH (1958) Epinephrine metabolites and pigmentation in the central nervous system in a case of phenylpyruvic oligophrenia. J Neurol Neurosurg Psychiat 21:58–62

    Google Scholar 

  • Følling A (1934) Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbíndung mit Imbezillität. Z Physiol Chem 227:169–176

    Google Scholar 

  • Friede RL (1975) Developmental neuropathology, Springer, New York Vienna

    Google Scholar 

  • Hsia YE (1976) Disorders of amino acid metabolism. In: Siegel GJ, Albers RW, Katzman R, Agranoff BW (eds) Basic neurochemistry. Little Brown Co., Boston, pp 521–524

    Google Scholar 

  • Jervis GA (1939) Genetics of phenylpyruvic oligophrenia (contribution to study of influence of heredity on mental defect) J Ment Sci 85:719–762

    Google Scholar 

  • Jervis GA (1953) Phenylpyruvic oligophrenia deficiency of phenylalanine-oxidizing system. Proc Soc Exp Biol Med 82:514–515

    Google Scholar 

  • Jervis GA (1963) Pathology. In: Lyman FL (ed) Phenylketonuria. Ch C Thomas, Springfield, pp 96–100

    Google Scholar 

  • Kimara H, McGeer PL, Pena F, McGeer EG (1980) Choline acetyltransferase-containing neurons in rodent brain demonstrated by immunohistochemistry. Science 208:1057–1059

    Google Scholar 

  • Konigsmark BW (1970) Methods for thercounting of neurons. In: Naunta WJH, Ebbesson SOE (eds) Contemporary research methods in neuroanatomy. Springer, New York Heidelberg Berlin, pp 315–340

    Google Scholar 

  • LaVelle A (1956) Nucleolar and Nissl substance development in nerve cells. J Comp Neurol 104:175–201

    Google Scholar 

  • Liss L, Grumer HD (1966) Effect of L. Phenylalanine on central nervous system elements in tissue culture. J Neurol Neurogurg Psychiat 29:371–374

    Google Scholar 

  • Loo YH, Fuiton T, Miller K, Wisniewski H (1980) Phenylacetate and brain dysfunction in experimental phenylketonuria: synaptic development. Life Sci 27:1283–1290

    Google Scholar 

  • Loo YH, Scotto J, Wisniewski HM (1978) Myelin deficiency in experimental phenylketonuria: contribution of the aromatic acid metabolites of phenylalanine. In: Palo J (ed) Myelination and demyclination. Plenum Press, New York London, pp 453–469

    Google Scholar 

  • Malamnd N (1966) Neuropathology of phenylketonuria. J Neuropathol Exp Neurol 25:254–268

    Google Scholar 

  • Martin J, Schlote W (1972) Central nervous system lesions in disorders of amino acid metabolism. J Neurol Sci 15:49–76

    Google Scholar 

  • Mesulam MM, Van Hoesen GW (1976) Acetylcholinesterase-rich projections from the basal forebrain of the rhesus monkey to neocortex. Brain Res. 109:152–157

    Google Scholar 

  • Nigam MP, Labar DR (1979) The effect of hyperphenylalanemia on size and density of synapses in rat neocortex. Brain Res 179:195–198

    Google Scholar 

  • Poser CM, Van Bogaert L (1959) Neuropathologic observations in phenylketonuria. Brain 82:1–9

    Google Scholar 

  • Prensky AL, Fishman MA, Daftari B (1971) Differential effects of hyperphenylalanemia on the development of the brain in the rat. Brain Res 33:181–191

    Google Scholar 

  • Robain D, Wen GY, Wisniewski HM, Shek JW, Loo YH (1981) Purkinje cell dendritic development in experimental phenylketonuria. Acta Neuropathol (Berl) 53:107–112

    Google Scholar 

  • Sander G (1951) Zur pathologischen Anatomie und Pathophysiologie des Gehirns bei der phenylpyruvischen Idiotie. Thesis, Zürich. Jasonpers Universiteits pers. Amsterdam. Cited by: Martin J, Schlote W (1972)

    Google Scholar 

  • Scholtz W (1957) Contribution a l'anatomie pathologique due systeme nerveux central dans l'oligophrenie phenylpyruvique. Encéphale 46:668–680

    Google Scholar 

  • Scriver CR, Clow CL (1980) Phenylketonuria: Epitome of human biochemical genetics. New Engl J Med 303:1336–1342

    Google Scholar 

  • Siegel GJ et al. (1976) Basic neurochimistry. Little Brown Co., Boston, pp 521–524

    Google Scholar 

  • Wen GY, Wisniewski HM, Shek JW, Loo JH, Fulton TR (1979) Neuropathology of phenylacetate poisoning in rats: An experimental model of phenylketonuria. Ann Neurol 7:557–566

    Google Scholar 

  • Williams RS, Hauser SL, Purpura DP, DeLong GR, Swisher CN (1980) Autism and mental retardation. Neuropathologic studies performed in four retarded persons with autistic features. Arch Neurol 37:749–753

    Google Scholar 

  • Yakovlev PI (1969) Development of the nuclei of the dorsal thalamus and of the cerebral cortex. In: Locke S (ed) Modern neurology. Papers in tribute to Derek Denny-Brown. Little Brown Co, Boston, pp 15–53

    Google Scholar 

  • Yakovlev PI (1970) Whole brain serial histological section. In: Tedeschi CG (ed) Morphological study of the nervous system by special methods. Little Brown Co. Boston, pp 371–378

    Google Scholar 

  • Yakovlev PI, Lecours AR (1967) The myelogenetic cycles of regional maturation of the brain. In: Minkowski A (ed) Regional development of the brain in early life. Blackwell, Oxford, pp 3–70

    Google Scholar 

  • Zelman IB, Czochánska-Kruk J, Borowicz K (1967) Neuropathologia fenylketonurii. Neuropat Polska 5:509–518

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ennice Kennedy Shriver Center for Mental Retardation, Waltham, MA, USA

    M. L. Bauman & Th. L. Kemper

  2. Chldren's Neurology Service, Massachusetts General Hospital, 02114, Boston, MA, USA

    M. L. Bauman

  3. Neuropathology Service, Boston City Hospital, 02114, Boston, MA, USA

    Th. L. Kemper

Authors
  1. M. L. Bauman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Th. L. Kemper
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by special fellowship, NSO 225301, NINDS (Dr. Bauman)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bauman, M.L., Kemper, T.L. Morphologic and histoanatomic observations of the brain in untreated human phenylketonuria. Acta Neuropathol 58, 55–63 (1982). https://doi.org/10.1007/BF00692698

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00692698

Key words

Search

Navigation