1. Heller T (1908) Ueber Dementia infantilis.  Zeitschrift für die Erforschung und Behandlung des
    Jugendlichen Schwachsinns 2:17-28
  2. Heller T (1930) Ueber Dementia infantilis.  Zeitschrift für Kinderforschung 37:661-667.
    Translation by Hulse WC (1954) in Journal of Nervous and Mental Diseases 119:471-477.
  3. DeSanctis S (1908) Dementia pracocissima catatonica oder Katatonie des frueheren
    Kindesalters?  Folia Neuro-Biologica, (Leipzig) 2:9-12.
  4. Kraepelin E (1904) Lectures on Clinical Psychiatry. Third English Edition, Johnston T, ed
    (1912).  New York:William Wood and Company.
  5. Kanner L (1943) Autistic disturbances of affective contact.  Nervous Child 2:217-250.
  6. Landau WM, Kleffner FR (1957) Syndrome of acquired aphasia with convulsive disorder in
    children. Neurology 7:523-30.
  7. Malamud N (1959) Heller's disease and childhood schizophrenia.  American Journal of
    Psychiatry 116:215-218.
  8. Ross IA (1959) An autistic child. Pediatric Conferences (Babies Hospital, Newark NJ) 2:1-13.
  9. Rogers SJ, Newhart-Larson S (1989) Characteristics of infantile autism in five children with
    Leber's congenital amaurosis. Developmental Medicine and Child Neurology 31:598-608.
  10. Creak M (1963) Childhood psychosis: A review of 100 cases. British Journal of Psychiatry 109:
    84-89.
  11. Williams RS, Hauser S, Purpura DP, deLong GR, Swisher CN (1980) Autism and mental
    retardation: Neuropathologic studies performed in four retarded persons with autistic
    behavior.  Archives of Neurology 37:748-753.
  12. Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A (1986) Lower
    Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC
    Autopsy Research Report. American Journal of Psychiatry 143:862-6.
  13. Courchesne E (1995) New evidence of cerebellar and brainstem hypoplasia in autistic infants,
    children and adolescents: the MR imaging study by Hashimoto and colleagues. Journal of
    Autism and Developmental Disorders25:19-22.
  14. Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, Harada M, Kuroda Y (1995)
    Development of the brainstem and cerebellum in autistic patients.  Journal of Autism and
    Developmental Disorders 25:1-18.
  15. Kemper TL, Bauman M (1998). Neuropathology of infantile autism. Journal of Neuropathology
    and Experimental Neurology 57:645-652 .
  16. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P (1998) A
    clinicopathological study of autism.  Brain 121:889-905.
3 -  Schizophrenia spectrum disorders
     The core syndrome of autism is a developmental
disorder present from birth; it is not progressive, and if
it is a chronic inborn error of aerobic metabolism, it is
not as severe as Landau-Kleffner syndrome, Rett
syndrome, or Leigh syndrome.  Heller (1908) and
DeSanctis (1908) described cases of disintegrative
disorder to which they both gave the name dementia
infantilis [1-3].  Selection of the term dementia
infantilis followed the nomenclature of Kraepelin
(1904) who presented many case reports of
premature mental decline to which he gave the name
dementia praecox [4].  Dementia praecox later came
to be known as schizophrenia.  Schizophrenia and
schizophrenia spectrum disorders might also be
described as disintegrative disorders of adolescence
or early adulthood.  Dementia infantilis came to be
known as Heller syndrome and many thought this to
be the same psychotic disorder described by Kanner
(1943) until a clear distinction was made between
autism present from birth and disintegrative disorders
[5, 6].  The papers of Malamud (1959) and Ross
(1959) reflect earlier descriptions of psychotic
disorders in children as either Heller’s syndrome or
autism [7, 8].

    Malamud (1959) described neuropathology in
three sets of siblings who all displayed signs of Heller
disorder [7].  All six of the patients he discussed
developed normally at first as in the case described
by Ross (1959); all followed a progressive course of
deterioration.  Widespread lipid deposits in the
neurons were found from the cerebral cortex to the
spinal cord on autopsy of a 10-year-old girl from one
pair of siblings, and a 7-year-old girl from another.  
The younger brother of the 10-year-old and younger
sister of the 7-year-old also displayed the same
progressive symptoms.  Based on the neuropathology
of the two children who died, a diagnosis of amaurotic
family idiocy was made for each pair of siblings.  
Amaurosis is a form of blindness, although cases of
amaurotic idiocy without amaurosis have been
reported. Rogers and Newhart-Larson (1989)
observed autistic behaviors in five children with
congenital amaurosis [10].

    The affliction of the third pair of siblings reported
by Malamud was fatal to both; the girl died at age 13
and the boy at age 11.  Symmetric bilateral lesions of
the corpus Luysi, mammillary bodies, and mammillo-
thalamic tracts were found.  The corpus Luysi
(subthalamic nucleus) provides inhibitory control for
the subcortical motor system in the basal ganglia.  
Malamud noted the similarity of the neuropathology in
the brains of these two children to that seen in
Korsakoff’s syndrome.  The symmetric brainstem
lesions of the corpus Luysi and mammillary bodies
noted by Malamud bear some similarity to lesions in
Leigh syndrome.  All of the children followed by
Malamud may have suffered from disorders of
mitochondrial energy production.  Lipid accumulation
within neurons may occur when fatty acid mobilization
is stimulated in response to aberrant oxidation of
glucose.

    Ross (1959) reported on the clinical course and
neuropathology of a child regarded to be autistic [8],
although it does not appear that she had the
developmental language disorder characteristic of
autism.  She had also been diagnosed as having
childhood schizophrenia.  She appeared to develop
normally until the age of two.  She became very
seasick on a voyage home to America from Australia
where her father had been stationed during World
War II.  It appears she may have suffered chronic
anorexia after that, which might have included a
deficiency of thiamine.  A succession of viral infections
between the ages of three and four were also noted.  
She died at age eleven, and the reported
neuropathology would seem to indicate Wernicke’s
encephalopathy.  Striking degeneration of the
mammillary bodies and anterior nuclei of the thalamus
were noted and cerebellar Purkinje cells were reduced
to half the normal number.

    Abnormalities in the brains of more recent cases of
autism are far less pronounced than in the child
discussed by Ross.  She might not have been
considered autistic by Creak (1963), Williams et al.
(1980), Ritvo et al. (1986), Courchesne (1995),
Hashimoto et al. (1995), Kemper and Bauman (1998),
or Bailey et al. (1998), but the similarity of the
subcortical pattern may be comparable to less severe
involvement of brainstem and cerebellar sites
observed in cases of true autism [10-16].  Ross’s case
might represent neurological impairment occurring
after normal language development that is
comparable to the perinatal event that leads to
autism.  Her brain was small, weighing 1017 grams as
compared to 1300 for an 11-year-old female.  Her
case does not exactly fit the description of Rett
syndrome, but could represent the result of a similar
pathological process leading to childhood
disintegrative disorder as distinct from infantile autism,
which is evident at a much earlier age.  The
neuropathology found in Ross' case might also
represent an example of Wernicke's encephalopathy
resulting from thiamine deficiency due to anorexia.
Full References
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References
  1. Heller T (1908) Ueber
    Dementia infantilis.
  2. Heller T (1930) Ueber
    Dementia infantilis.   
    Translation by Hulse WC
    (1954)
  3. DeSanctis S (1908)
    Dementia pracocissima
    catatonica oder Katatonie des
    frueheren Kindesalters?
  4. Kraepelin E (1904) Lectures
    on Clinical Psychiatry.
  5. Kanner L (1943) Autistic
    disturbances of affective
    contact.
  6. Landau WM, Kleffner FR
    (1957) Syndrome of acquired
    aphasia with convulsive
    disorder in children.
  7. Malamud N (1959) Heller's
    disease and childhood
    schizophrenia.
  8. Ross IA (1959) An autistic
    child.
  9. Rogers SJ, Newhart-Larson
    S (1989) Characteristics of
    infantile autism in five
    children with Leber's
    congenital amaurosis.
  10. Creak M (1963) Childhood
    psychosis: A review of 100
    cases.
  11. Williams RS et al. (1980)
    Autism and mental
    retardation: Neuropathologic
    studies performed in four
    retarded persons with autistic
    behavior.
  12. Ritvo ER et al. (1986) Lower
    Purkinje cell counts in the
    cerebella of four autistic
    subjects: initial findings of the
    UCLA-NSAC Autopsy
    Research Report.
  13. Courchesne E (1995) New
    evidence of cerebellar and
    brainstem hypoplasia in
    autistic infants, children and
    adolescents: the MR imaging
    study by Hashimoto and
    colleagues.
  14. Hashimoto T et al. (1995)
    Development of the
    brainstem and cerebellum in
    autistic patients.
  15. Kemper TL, Bauman M
    (1998). Neuropathology of
    infantile autism.
  16. Bailey A et al. (1998) A
    clinicopathological study of
    autism.
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