Down's Syndrome Children with Autistic Features

Mary Coleman, M.D.
Down's Syndrome. Papers and Abstracts for Professionals
Volume 9, No. 3, pp. 1-2, July 1986
  Reprinted with the permission of Mary Coleman, M.D.
Editor, Down's Syndrome. Papers and Abstracts for Professionals

There is virtually no literature describing Down's syndrome children who have autistic features. Yet everyone who runs a Down's syndrome clinic occasionally sees a child of this type. This paper discusses an approach to the diagnosis and treatment of such a youngster.

Down's syndrome occurs in of between 1.0-1.2/1000 live births (Hook, 1982) while the autistic syndrome occurs between .4-.5/1000 live births (Torrey et at. 1975). Thus both Down's syndrome and the autistic syndrome are among the more common forms of mental handicaps seen in children.

One of the important questions on evaluating a child is to try and determine whether both disease entities have occurred coincidentally in this child or whether this child's autistic symptoms stem from an unusual effect of the addition of an extra twenty-first chromosome to the child's cells. One example of the double diagnosis occurs in Down's syndrome children who develop the infantile spasms syndrome associated with hypsarrhythmia. Patients, Down's or otherwise, who develop infantile spasms are often left with autistic features.

Clinical Delineation of a Child with Both Syndromes

To start with, it is necessary to define a Down's syndrome child with autistic features. Such a child can be diagnosed if the child, in addition to having a Trisomy 21 chromosomal karyotype (or one of the other chromosomal variants that result in the phenotype of Down's syndrome), the child also has two or more of the following disturbances:

  1. Significant disturbance of social relatedness to parents and peers, with poor eye contact and a sense of "aloneness."
  2. Repetitive routines such as lining up objects and insisting on the sameness of certain clothes or certain foods or certain spaces between objects at the time of eating, etc. These children also may have a fascination with spinning objects such as wheels of toy cars or records, bizarre attachments to certain objects such as stripes, pins, pieces of plastic toys.
  3. Unusual, inconstant, sensory responsiveness. This can be seen in children who may appear deaf in one minute and overly sensitive to sound at another. Another example is a child who often shrinks from a touch but sometimes enjoys being tickled very forcefully.
  4. A child who, in spite of his general level of retardation, has an islet of special ability at a completely different level that other levels of mental functioning. These skills may be in music, art, jigsaw puzzles or other visual spatial skills.

Evaluating autistic features in a Down's syndrome child can be quite difficult. If the child, for example, appears not to be hearing well, it may not be due to an autistic feature but may be due to otitis media (middle ear infection) a common problem seen in Down's syndrome children. A child who is irritable, withdrawn, with poor eye contact may be a child who is developing a hidden infection such as in the bladder, the middle ear or other infectious more commonly seen in a Down's syndrome child. Thus the diagnosis of autistic features should only be made if it is a consistent pattern over a considerable period of time where any infectious or other etiologies have carefully ruled out.

Medical Evaluation

Assuming that the diagnosis has been made of a Down's syndrome child with autistic features, then a medical evaluation is indicated. The autistic syndrome is not a single disease but a syndrome of many different etiologies. A description of a full workup for a child with an autistic syndrome is found in the book The Biology of The Autistic Syndromes (Coleman and Gillberg, 1985).

This paper is presented to indicate that it is not necessary to immediately move toward psychotropic drugs in treatment of behavior disorders with Down's syndrome children. As with any other individual, each child needs to have a specific clinical evaluation with the type of symptomology studied. For example, the tendency to place retarded children with poor attention span on stimulant drugs (pharmacological agents known to make autism worse in some cases) should be avoided until the child has had an adequate workup. Gladow (1985) discusses this problem in some detail.

In this paper I am going to give two examples of Down's syndrome children with autistic features who were found to gave a metabolic disease entity concomitantly seen in the autistic syndrome. Although, in both cases identification of the problem appeared to have helped with the management of the child, it should be noted that single case histories are never conclusive. However, the problem of identifying enough patients to perform double blind studies in these rare combination syndromes is a major drawback to scientific advance in this field.

Purine Abnormalities in Down's Syndrome and the Autistic Syndrome

Elevation of the uric acid both in the blood and in the urine of Down's syndrome patients has been an area under study for a long time (Pueschel, 1982). There have been many articles on the subject, a number puzzling over the fact that the hyperuricenna seen in Down's syndrome is less likely to result in gouty arthritis than in other individuals. Recently, using recombinant DNA techniques it has been determined that two of the genes involved in purine biosynthesis, phosphoribosyl-glycina-mide synthetase (PRGS) and phosphofructokinase (PFKL) are located on the 21st chromosome (Smith and Warren, 1985). It is much too early to know if these genes are the ones responsible for purine over-production in Down's syndrome, whether there also are modifying genes etc.

Three enzymes — 5-phosphoribosyt-l-pyrophosphate (PRPP synthetase), inosinate dehydrogenase and adenyl-osuccinate lyase — are enzymes in the purine pathway known to be abnormal in one of more autistic children. Some of these enzyme errors have experimental treatments available.

Thus, in evaluating a Down's child with autistic features, a uric acid clearance may be valuable. Even if it is not possible to pin down the exact gene or enzyme involved in a child, if the child is a purine overexcretor then dietary measures reducing purines or allopurinol can be tried in an effort to diminish autistic features. There are no double blind studies showing that these treatments are of value. In one 10-year-old boy with Trisomy 21 in my practice, such a diet and allopurinol appeared to make a difference in the child's attention span and ability to learn. It may or may not be coincidence that the child's clinical picture improved on the diet and allopurinol and deteriorated during two crossover periods off the diet and on placebo.

Lactic Acidosis in Down's Syndrome and the Autistic Syndrome

Lactic acidosis or hyperlactatemia without acidosis in a child indicates some abnormality in the utilization of sugar, which increases the rate of lactate production relative to lactate utilization. There is a paper in the literature describing lactic acidosis in a Down's syndrome child (Hartman et al. 1962). In my practice, there was a 3-year-old boy with Trisomy 21 who had a very poor attention span and a number of autistic features. The child was found to have lactic acidosis on repeated testing. Studies are currently underway in attempts to find, if possible, which enzyme is involved in the carbohydrate pathway in this child. Placed on a low carbohydrate diet and thiamin, the child's attention span and language showed marked improvement, with some evidence of deterioration or plateauing during two crossover periods. Again, no double blind studies have been done to confirm these results and, since a specific enzyme has not even been identified in this child, these results are most preliminary.


Down's syndrome children like other individuals have psychiatric symptoms. They can appear autistic or become anxious, depressed, anorexic or psychotic (Keegan et al. 1974; Semansky and Betelman 1984). The solution to helping children lies in thinking of them as individuals who also happen to have Down's syndrome and attacking the problem on an individual basis using individual medical therapy as appropriate. For the Down's syndrome child with autistic features, individual evaluation is particularly important.

We have the power to enhance the quality of life and the future of Down's syndrome individuals if we treat them with the care and attention each child deserves.


  1. G.F. Smith and S.T. Warren. 1985. "The Biology of Down Syndrome", a chapter in Molecular Structure of the Number 21 Chromosome and Down Syndrome, G.P. Smith (ed) Annals of the New York Academy of Sciences. vol. 450, New York.
  2. M. Coleman and C. Gillberg. 1985. The Biology of the Autistic Syndromes. Praeger Scientific, New York.
  3. K. Gadow. 1985. Prevalence and Efficacy of Stimulant Drug Use with Mentally Retarded Children and Youth. Psychopharmacology Bulletin (NIMH) 21:291-303.
  4. A.F. Hartman, H.S. Wohitmann, M.L. Purkerson and M.E. Wesley. 1962. Lactate metabolism—studies of a child with a serious congenital deviation. Journal of Pediatrics. 61:165.
  5. D.L. Keegan, Z. Parker and A. Pettigrew. 1974. Psychosis in Down's Syndrome treated with amitriptyline. Canadian Medical Journal. 110:1128-1131.
  6. S.M. Pueschel and J.E. Rynders. 1982. Down Syndrome: Advances in Biomedicine and the Behavioral Sciences. The Ware Press, Cambridge, Mass.
  7. L.S. Szymanski and J. Biederman. 1984. Depression and Anorexia Nervosa of Persons with Down Syndrome. American Journal of Mental Deficiency. 89:246-251.
  8. E.F. Torry, S.P. Hersh and K.D. McCabe. 1975. Early childhood psychosis and bleeding during pregnancy; a prospective study of gravid women and their offspring. Journal of Autism and Childhood Schizophrenia. 5:287-297.