PLASMA AMINO ACIDS IN AN AUTISTIC GIRL, FIRST AND AFTER 7 YEARS OF PHARMACOTHERAPY.

Renato COCCHI, a neurologist and a medical psychologist.

(Italian translation) // Testo in Italiano

Summary.

Plasma amino acids of a female child with an early onset Pervasive Developmental Disorder, were compared before and after a 7-years pharmacotherapy started when she was four-years. The improvement in the plasma amino acid condition parallels a net improvement in the subject's behaviour although language deficit and mental retardation do persist. The relationship between these events is not however clear

Key words: Pervasive Developmental Disorder; pharmacotherapy; plasma amino acids; follow-up

Autism

Drug modulation of stress reactions

Mental retardation

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The rating of the plasmatic amino acids in autistic subjects would be a tool to redirect a pharmacotherapy in this heavy childhood illness. For which there are always increase confirmations of a basic biological trouble. I have the rates of the plasmatic amino acids of an autistic child, in the 1981 and in the 1989, first and after seven years and still lasting pharmacotherapy. This allows us to present the results with the results on the intellectual, emotional and social behaviour.

Case history.

Girl, born in 1977. During her birth she had pre-delivery bleeding and pharmacological induction, after an abortion threat at three months of pregnancy and a premature delivery threat at five months. Three convulsive fits happened in the first years. She had a still troubled EEG when she was four years and four months, when she came to my outpatients' for the first consultation. She was taking drug therapy with phenobarbital, gamma-hydroxybutirate plus cycles of a compound of cerebral phospholipids, pyridoxine and cyanocobalamin. She had the diagnosis of autism, better termed now, according to DSM-III, R, as Early Onset Pervasive Developmental Disorder.

I recorded the following symptoms during the first examination: - Social isolation, - motor and oral stereotypies, - a profound linguistic deficit, - need for sameness, - a gaze aversion, - sensory hypersensitivity, - sudden mood changes, - unmotivated anxiety, - paper ripping, - the use of the hand of the other as a tool to take objects, - aggression and hyperactivity, - null object relationship.

Till the January 1989, when she has done the two checkups of the plasmatic amino acids, she has assumed the following drugs, but in different times, and in various combinations: - glutamine, - carbamazepine, - vitamins B1, B6, B12, - diazepam, - 5-hidroxytriptophan, - clonidine, - viloxazine, - acetil-carnitine, - amitriptyline, immediately stopped, - pyritinol, - SAMe, - dibenzothiazepine, - delorazepam, all at small dosages. When she had her second checkup of the plasmatic amino acids, she was taking: - SAMe 300mg, - pyritinol 100mg, - carbamazepine 100mg, - clonidine 100mcg, - diazepam 2mg; - dibenzothiazepine 3.3mg.

Missing symptoms: - Gaze aversion, - Aggression and hyperactivity, - unmotivated anxiety, - sudden mood changes, - need for the sameness - sensory hypersensitivity. Moreover, she showed discreet object relationship.

Decidedly reduced symptoms were: - social isolation, - motor stereotypies, - echolalia; but produced language was poorly improved; moderate to severe mental retardation, increased by the age, was also present.

Table 1: plasmatic amino acids (mg% / ml) first and after pharmacotherapy.

Amino acid	Confidence limits	1° to check	2° to check	Variation
Taurine	0.35 - 0.91	0.56	0.6
Aspartate	0.00 - 0.21	0.29 (*)	0.2	normalized
Treionine	0.95 -1.95	1.56	1.3
Serine	0.54 - 1.62	1.37	0.7
Asparagine	0.33 - 0.89	Not measurable ( D)	0.6	measurable/normal
Glutamate	0.10 - 1.10	4.31 (*)	1.0	normalized
Glutamine	6.41 - 11.65	13.45(*)	1.2	from excess to deficit
Proline	1.02 - 4.06	2.00	1.6
Glycine	0.59 - 1.79	2.21 (*)	1.1	normalized
Alanine	2.03 - 4.63	4.23	2.1
Citrulline	0.27 - 1.11	0.88	ND	from normal to not meeasurable
Alpha-amino butyrate	0.07 - 0.39	0.26	ND	from normal to not measurable
Valine	1.71 - 3.95	1.78	2.0
Cystine	0.36 - 1.92	ND	0.6	measurable/normal
Methionine	0.18 - 0.45	0.22	0.2
Isoleucine	0.43 - 1.19	0.40 (*)	0.7	normalized
Leucine	1.00 - 2.36	0.90 (*)	1.3	normalized
Thirosine	0.68 - 1.60	1.47	1.3
Phenylalanine	0.52 - 1.28	0.55	0.7
Tryptophan	0.71 - 1.47	0.95	0.8
Ornithine	0.79 - 1.23	0.46 (*)	0.8	normalized
Lysine	1.82 - 314	1.18 (*)	1.6 (*)
Histidine	0.80 - 2.20	1.02	1.3
Arginine	0.47 - 2.07	0,96	0.6

(*) out of from confidence limits Table 2: statistics.

State	1° check	%	2° check	%	Difference	%
Normal	14	58.3	20	83.34	+6	+25.00
In excess	4	16.6	0	0.00	-4	-16.6
In defect	4	16.6	2	8.33	-2	-8.33
Not measurable ( ND)	2	8.33	2	8.33	0	0.00
Totals	24	100.00	24	100.00

Chi Square = 5.72 with 3 df, NS.

The contextual rating of 29 urinary amino acids or their compounds, done with the second check, did not point out rates out of the norm.

Discussion.

It is not easy to interpret these data and try to correlate them with the clinical course of the illness. It has to exclude, currently, a some thesaurismosis' form, since the normal urinary excretion. I think it was even nearly impossible that she had an initial abnormal urinary excretion of some amino acids or their compound. So because every thesaurismosis, at least for what we known now, has a genetic base. We need to note, the disappearance or reduction so many symptoms.

Besides the accumulated mental retardation, we note also the remaining of a serious deficit of the productive language and of some social impairment. But we found even an improvement of the plasmatic amino acids, whose normal set ran from 58.33% to 83.34%. It seems unknown which is the relationship between blood amino acids and their brain equivalents.

The excess or the defect of an amino acid in the blood does not surely mean the same state in the brain. Even the opposite can equally be right. In other words, an excess of plasmatic glycine could correspond to an excess of active and available brain glycine. It can correspond even to his deficit of use being the related receptors out of work. So it could beckwards happen a stop of this amino acid crossing the blood-brain barrier. So, a deficit of plasmatic glutamine could even correspond to its increased brain turnover.

Waiting these mechanisms clarified, we may at least suppose that a normal rate of a certain blood amino acid has an increased probability to correspond to a normal brain use of it. Therefore, in our case, the improved blood amino-acids' rates can easy have some links with the improvement of the brain working and the consequent behaviour. It is even possible that what seems me of difficult interpretation, refined biochemistrists can better understand by comparing the role of amino acids within and outside the central nervous system.

Nevertheless, I do not have information about researchers that could own a global vision of these complex interrelations. As for my therapeutic work, the premises of which I set up (Cocchi, 1990 ), data here reported do not deny it. In particular it happens so for my hypothesis of a possible brain glutamergic hyperactivity. I do not know any limiting step of the brain glutamine transformation into glutamate. Only glutamine crosses the blood-brain barrier, while the glutamate and the plasmatic glutamine can transform into each another (Meister, 1956 and 1969).

The previous glutamate and glutamine blood excess and the final normal rate of the glutamate with a deficit of glutamine suggest that this mechanism had, probably, a better regulation by the drugs used.

Of other hand, even the initial excess and following normalization of aspartate, as another amino acid with excitatory properties in the brain, seems to drive towards the same interpretation. Anyhow, we are dealing with initials and very rough findings, for a surely complex syndrome, and nearly certain of multifactorial nature.

Without any doubts we cannot understand the relationship between blood and brain amino acids as for now. Then, to allocate therapeutic programs on such findings does not seem a justifiable choice, but in forms of childhood psychoses by thesaurismoses.

By saying so, I cannot deny that investigation of the blood amino acids is a pathway to walking. But we still do not know the full use of picked data. The hope that they "speak" by themselves, out of any preliminary hypothesis of explanation, is a method that had already confutation since decades in the experimental field. Data picking up and their statistic treatment will however do new ease formulation of suggestions to verify (Fortini, 1989).

References

Cocchi R.: The pharmacological approach to treating childhood psychoses: A theoretical basis. It. J. Intellect. Impair. 1990, 3: 185-193.

Fortini P.: Darwin, Lamarck e l'autismo. Bollettino ANGSA 1989, 2/4-5: 2-6.

Meister A.: Metabolism of glutamine. Physiol. Rev. 1956, 36: 103-127.

Maister A.: On the synthesis and utilisation of glutamine. Harvey Lect. 1969, 63: 139-168.

First translated in English and published on Internet on June 2002. Copyright by Renato Cocchi, 2002.

Author's address: dr Renato COCCHI, via Rabbeno, 3
42100 Reggio Emilia (Italy)

renatococchi@libero.it

Italian translation // Testo in italiano

Autism

Drug modulation of stress reactions

Mental retardation

Home Page // Pagina iniziale