We have been measuring pancreatic enzymes in the stool for 8 years: chymotrypsin directly and amylase and lipase indirectly. About 15% of autistic spectrum patients were deficient therein; they were given capsules containing these 3 enzymes, plus 2 additional ones (bromelain and papain) in a neutral solution. This group improved initially and continued to do so as normal enzyme levels were attained.

Of the other 85% of autistic spectrum children seen here over the last 8 years, THE VAST MAJORITY HAD NORMAL STOOL ENZYME LEVELS to begin with. About 10% had high levels; administration of this preparation to 3 volunteers with normal levels and 3 with elevated levels resulted in marked exacerbation of all symptoms, especially of hyperanxiety in the former group, and no effect in the latter group. With IV secretin after several monthly injections (cost $170/ampoule), apparently a small percent improve transiently, some have exacerbations, and in most there is no significant behavioral or cognitive change. Estimates by some non-M.D.'s that 70% of patients improve are GROSSLY MISLEADING. If the patient does not improve or in instances when he/she gets worse, the parent generally does not return to the physician, and conveys no information to him. Thus the total sample size is necessary to determine the percentage who were helped. In the case of previous years' fads in approaches to therapy of autism, e.g., Intravenous Immunoglobulin (IVIG), ONLY ABOUT 15% WERE HELPED. These turned out to be the same types in whom we found AUTOANTIBODIES TO MYELIN BASIC PROTEIN and other Central Nervous System tissue constituents. THE OTHERS WERE NOT HELPED. Indeed, some developed increasingly severe anaphylactic reactions due to infusion of foreign isotypes of IgG and IgA (the Ig is isolated from pools of 600 to 10,000 donors, so it contains foreign IgG-Gm and IgA-Am isotypes, which can induce antibody formation much like Rh+ red cells repeatedly infused into Rh- individuals).

Two known deaths due to anaphylaxis have occurred using IVIG. Immunostaining methods detected immune complexes containing host antibodies and "donor" allotypes in the perivascular spaces in the bronchioles, and histologic examination showed the typical changes of anaphylaxis. The physician administering the IVIG thought he had a 50% improval rate; the parents of the 15% who improved responded with letters of thanks, and about 15% of parents of nonresponders wrote: a small percentage of the 85% nonresponders.

It is notable that the company making the product, Farrington Pharmaceuticals, is discontinuing it because of progressive decrease in demand, a far better parameter of its "success" rate than anecdotal observations.

Within a few months after the secretion infusions began, parents of autistic children began phoning this office because they had heard that I did not advocate pancreatic enzymes for more than a small percent, measured these before deciding whether enzymes would help, gave them only to patients deficient therein, and these had had no adverse reactions. Parents were phoning to complain that they had been told by others that the material was completely safe and would help the majority of children—no matter in which part of the "autistic" spectrum they were, including Asperger’s, Landau-Kleffner, Attention Deficit Disorder, Delayed Developmental Disorder, Pervasive Developmental Disorder, etc. Thus we do not know whether those who improved belonged to only 1 of the 8+ subsets of this syndrome, each of which has a different etiology and therefore requires a different therapy.

As indicated, intravenous secretin infusion made a small percent of the patients better and a similar percentage worse. Is it not folly to administer this material without prior check of the enzyme levels? In patients with congestive heart failure, similar symptoms occur with insufficient digoxin as do with digoxin toxicity, namely anorexia, nausea, malaise, difficulty breathing. Would you blithely give a patient with these symptoms more digoxin, or would you obtain a plasma digoxin level before deciding (only 5 hours of wait time for report)?

Especially appalling is the conclusion drawn: that secretin deficiency is the cause of autism! Those making such judgments cannot distinguish between cause, effect, and ancillary feature. Defective pancreatic enzyme production usually occurs because of a sequence of events (see "Typical Course of Autistic Patient") beginning with use of anti-BACTERIAL antibiotics for the recurrent VIRAL otitis media (usually due to Respiratory Syncytial Virus), which often occurs because of the impairment in cell-mediated immunity induced by multiple immunizations, beginning currently at 12 hours of life and continuing almost monthly till 15 months. These antibiotics eradicate the helpful bacteria lining and protecting the wall of the large bowel (bifidobacteria and lactobacilli vulgaris and acidophilus), thus predisposing to Candidiasis. Treatment of the latter with conventional synthetic antifungal agents often causes impairment of liver detoxification functions, and decrease in synthesis of phosphosulfotransferase, an enzyme necessary to cleave food proteins, e.g. casein, into smaller easily absorbable peptides. The alteration in pH in the large intestine may lead to constipation, with casein at the center of an increasingly large fecal mass and production of caseomorphines, which are responsible for the cognitive impairment in these individuals.

NIH double-blind studies of efficacy of secretin in treating autism are underway in several University hospitals. (Did these pass through a study section? If so, were any hard scientists involved? Or merely psychologists and pediatricians, who have never had formal laboratory training and thus never learned how to properly collect and evaluate data, including clinical data, on a rational basis, rather than an impulsive one?)

This latest fad is typical of the "Let’s give it to every patient" approach common in the therapy of autism, due to failure to recognize obvious differences demonstrable by laboratory tests. Thus every year or two a new fad has emerged which holds a smaller percent of patients:

1. Orthomolecular doses of vitamins B1, B6, and B12: various pathogenic bacteria compete avidly with the body for such products. Granted, too much of all of these would not produce damage, but if a selective absorption defect for B12 exists, so that the body folic acid / B12 ratio were very high, dangerous neurologic disease could ensue.
   


2. Antifungal antibiotics: 12-18 months of therapy, given to all -- even children without evidence of Candida in colon, urine, saliva, or serum.
   


3. Dimethylglycine (DMG): A small percent of autistic spectrum patients have methylation defects due to deficient methyl groups; the Autism Research Institute, San Diego, has in the past advocated DMG for all autistic spectrum patients. The methylation defect, when present, can cause a defect in sulfation. However, this is measurable, and if present, trimethylglycine (betaine) will provide more methyl groups and in addition decrease the abdominal complaints present in patients with such deficiency. MTM, the active catabolic product of dimethyl sulfoxide, is even more effective as a methyl donor, also has beneficial cognitive effects, and helps relieve muscle symptoms if present.
   


4. IVIG: See above; only useful in autoimmune autism due to molecular mimicry (about 15% of patients). Repeated infusion may cause anaphylactic reactions due to production of antibodies against foreign allotypic determinants on antibody molecules.