Derrick Lonsdale

Dysautonomia in autism spectrum disorder: case reports of a family with review of the literature.

Case histories of a mother and her two children are reported. The mother was a recovered alcoholic. She and her two children, both of whom had symptoms that are typical of autistic spectrum disorder, had dysautonomia. All had intermittently abnormal erythrocyte transketolase studies indicating abnormal thiamine pyrophosphate homeostasis. Both children had unusual concentrations of urinary arsenic. All had symptomatic improvement with diet restriction and supplementary vitamin therapy but quickly relapsed after ingestion of sugar, milk, or wheat. The stress of a heavy metal burden, superimposed on existing genetic or epigenetic risk factors, may be important in the etiology of autism spectrum disorder when in combination. Dysautonomia has been associated with several diseases, including autism, without a common etiology. It is hypothesized that oxidative stress results in loss of cellular energy and causes retardation of hard wiring of the brain in infancy, affecting limbic system control of the autonomic nervous system.

A Clinical Study of Secretin in Autism and Pervasive Developmental Delay

Purpose: The aim of this study was to examine the clinical effect of a single dose of secretin given to patients whose disease status lay within the autistic spectrum. Design: Open, uncontrolled trial. Materials and Methods: Sixty-four patients were registered for the study. They included 3 female adults and 2 male adolescents. There was a total of 16 dropouts. Thus there were 48 evaluable patients. Each patient received a complete vial of secretin, irrespective of current age and body weight. Any existing treatment that had already been started before the study began was allowed to continue. No new treatment was permitted for a minimum period of 8 weeks when study surveillance was completed. The parents or guardians performed clinical assessment on a weekly basis, using numerical scoring of symptoms in a questionnaire. The only laboratory study performed was a hair analysis at the outset and at the completion of the 8 weeks of surveillance. Results: Of 48 evaluable patients, there were 39 whose clinical ...

TREATMENT OF THREATENED S.I.D.S. WITH MEGADOSF THIAMINE HYDROCHLORIDE

Steinschneider presented good evidence that infants who died suddenly and unexpectedly frequently have premonitory symptoms which enable the alert physician to recognize the danger (Pediat 50:646, 1972). Fehily (Br. Med. J. 2:590, 1944) described a syndrome of sudden death in Chinese infants in Hong Kong called “breast milk toxicity syndrome”. It commonly occurred in infants who were breast fed by their B1 avitaminotic mothers and was related to caloric intake. When maternal calorie intake was forcibly reduced by Japanese invaders, the syndrome disappeared. It reappeared when rationing of rice was discontinued. Rarity of the syndrome under the age of 1 month and over 5 months, a peak incidence at 3-4 months, predilection for “well nourished” males, higher incidence in early spring, death during sleep and lack of autopsy histopathology, were identical to the epidemiology of modern S.I.D.S. with the exception of breast Vs bottle feeding. Japanese investigators showed that thiamine deficiency produced autonomic dysfunction and detected histopathology within the central and peripheral components of the system. In 9 infants within this age group, symptoms of autonomic dysfunction suggested candidacy for S.I.D.S. and included life threatening apnea in all. Monitoring in hospital confirmed the symptoms. All of the infants were treated with thiamine hydrochloride, varying from 30 to 300 mg/day. No damaging side effects were seen and symptoms disappeared rapidly in all. All are well in follow up and only 2 have remained extensively dependent upon thiamine.

AMINOACIDURIA AS AN INDICATOR OF PHENYLAIANINE AND|[sol]|OR CALORIC DEFICIENCY IN TREATED PKU PATIENTS

Successful treatment of phenylketonuria (PKU) depends upon neonatal diagnosis and optimum combination of dietary phenylalanine and calories, especially in the first 3 months. Head circumference increases and “catch up” growth occurs with such dietary optimum. This acceleration requires appropriate changes in dietary phenylalanine and calories. Low serum phenylalanine concentrations (<2 mg/100 ml) indicate increased phenylalanine requirement but increased caloric needs are harder to determine. Of 19 infants with PKU, identified by neonatal screening and treated by phenylalanine restriction since January 1967, 15 excreted increased amounts of urinary amino acids, usually glycine, alanine, methionine and phenylalanine, but occasionally others as well. Unappeased appetite, deceleration in head circumference change, and amino-aciduria were usually corrected by increasing dietary phenylalanine. In some cases, when the serum phenylalanine was high, improvement in these criteria was accomplished by increasing dietary calories without increasing phenylalanine intake. Diet prescriptions during the first 3 months required phenylalanine increases to as high as 125 mg/Kg body wt. and calories to as high as 185/kg. Appropriate decreases were possible after 4 to 6 months and allowances per unit body wt. were usually stable after 1 year. Aminoaciduria appeared to reflect an improper dietary balance.

Pyruvic decarboxylase inhibition in ketoaciduria

A patient with intermittent episodes of cerebellar ataxia has been described (Pediat. 43:1025, 1969). The child excreted large amounts of urinary pyruvic acid during an episode which was studied in detail. Fibrobalst tissue culture cells were assayed for pyruvic decarboxylase and found to contain a low concentration of this enzyme. further examination of urine collected during the ataxic episode revealed that alanine was excreted in amounts proportional to that of pyruvic acid and that both metabolites were in concentrations inversely proportional to those of glutamic acid and aspartic acid. A child with late diagnosed, and hitherto untreated, phenylketonuria (PKU) was examined and found to have a high serum phenylalaline concentration and ketoaciduria. She was treated with a phenylalanine deprivation diet and urines collected in day and night 12-hour contiguous sequence. As the serum phenylalanine concentration fell there was a concomitant decrease in greatly elevated concentrations of urinary pyruvic acid into the normal range tother with a steady increase in concentrations of urinary glytamic acid. These observations suggested that inhibition of pyruvic decarboxylase could be an important mechanism in PKU as well as other ketoacidurias and that such a mechanism might involve the metabolism of glutamic acid. Experiments were carried out and showed that authentic α iso caproic acid and phenylpyruvic acid produce a marked decrease in the activity of pyruvic decarboxylase in vitro.