The Nutritional Aspects
of Rett Syndrome
Marylynne A. Rice, RD; Richard H. Haas, MD
Abstract
Nutrition is a major problem for the Rett patient. We have studied 21 girls with Rett syndrome (19 typical, two atypical).
We report our experience in this population with the nutritional aspects of Rett syndrome, the typical dietary habits,
and various nutritional deficiencies. Further experience with the use of high fat diets is reported. (J
1988;3(Suppl):S35-S42).
expanding knowledge in the field of Rett
Thesyndrome reflects cumulative efforts from
around the world. Great strides have been made in
the last 4 years in developing diagnostic criteria and
defining the clinical presentation of this previously
unrecognized diseases. 1-5
It has become clear that the typical Rett patient is
usually thin and often growth-retarded. Beginning
with Dr Andreas Rett’s description of his original 22
patients, the typical Rett patient has been reported as
malnourished and nutritionally at risk.6 Naidu et al
have reported ongoing weight loss and reduction of
muscle mass as a major concern during the growth
period from 5 to 15 years of age.3
This clinical pre-
sentation with growth failure has been supported by
additional investigators, and appears to represent
one of the characteristic features of the typical or
classic Rett patient. 3,5,1,8
Cachexia is clearly a cause of
9
death in some Rett patients.9
Although severe growth and weight retardation
is usually seen, not all Rett patients present in this
manner. Holm’ found in her study of 21 girls that
linear growth retardation was present in 48% of the
patients. An additional 38% had a fall in height per-
centile in the first few years of life.’ Haas et al
reported an atypical or forme fruste patient present-
ing with appropriate height and weight, and sub-
sequently we have seen additional atypical patients
with normal weight.l° Such observations raise the
From the Departments of Clinical Nutrition, Neurosciences,
and Pediatrics, University of California, San Diego.
Address correspondence to Dr Richard H. Haas, Division of
Pediatric Neurology, H-815B, UCSD Medical Center, 225 Dickin-
son Street, San Diego, CA 92103.
Child
Neurol
question of whether the malnutrition and growth
retardation observed in Rett patients is an inevitable
part of the disease process, or the result of inadequate
or inappropriate nutritional support.
Many disease states impose specific nutrient
requirements as a result of an alteration in either
digestion, absorption, or metabolism. Knowledge of
the disease process and its metabolic consequences is
a
prerequisite for fully understanding the nutritional
implications of a disease. Presently the etiology of
Rett syndrome is unknown. Underlying genetic or
metabolic defects appear promising possibilities.
Knowledge of the exact mechanism would be helpful
in predicting nutrient deficits and requirements, but
until this disease is better understood an empirical
approach is necessary.
Dietary intakes can be evaluated and compared
to &dquo;normal&dquo; standards; however, application of these
standards for developmentally delayed children is
difficult at best.l1-13 Nutritional standards and a di-
etary profile (with its health-related implications) are
needed to develop the appropriate dietary interven-
tion for the Rett patient. Haas et al reported that the
unmodified home diet contained 126 kcal~’kg in the
seven patients studied.l° The ratio of constituents-
18% protein, 42% carbohydrate, and 38% fat-rep-
resented a normal American diet. Despite this docu-
mented high calorie intake only one of the seven
patients studied had gained more than 1.1 kg in
the preceding 2 years. In this paper we describe the
nutritional profile of our expanded population, pre-
sent follow-up data on the four out of the seven original
patients who remained on a high-fat diet, and report
our further experience with the nutritional manage-
ment of Rett syndrome.
S35
Methods
Twenty-one female patients with Rett syndrome
between the ages of 2 and 24 years were followed
through the pediatric neurometabolic clinic. Several
of these patients were followed for more than 3 years
and represent original subjects reported in 1985, while
others have only recently been diagnosed.10 The
patients evaluated were classified according to the5
stages suggested by Hagberg and Witt-Engerstrom.5
One patient was in stage II, 12 in stage III, and eight
in stage IV. Nineteen patients were considered typi-
cal and two were atypical based on 1985 criteria and
subsequent reports. 2,4,14,15
Upon initial referral to the pediatric clinic all pa-
tients received a complete neurologic examination, a
battery of biochemical tests, video-taping, psychologic
evaluation, and nutritional assessment. The biochemi-
cal tests included urine metabolic screening as well as
amino and organic acid quantitation where possible.
Blood tests included complete blood cell count (CBC),
differential count, platelet count, blood film, BUN,
electrolytes, calcium, phosphorus, ammonia, lactate,
pyruvate, bilirubin, SGOT, and SGPT. Cholesterol,
high-density lipoprotein (HDL), and triglyceride
levels were measured in all patients studied in the
last 12 months. The nutritional assessment included
a diet history questionnaire, anthropometrics, and
24-hour diet recall. Computer nutrient analysis of the
diet recall was performed using the Nutritionist III
TABLE 1
Methods of Dietary Intervention for Rett Patients
RDAs =
Recommended Dietary Allowances.
S36
database. 16 The subjective information (ie, appetite,
derives pleasure from food, etc) was obtained by
personal interview with the principal caretaker, who
was usually the mother. The capacity to self-feed was
defined as the ability to put food into the mouth un-
assisted. The patients were followed semiannually or
more frequently, at which time the interview, dietary
assessment, physical examination, psychologic evalu-
ation, video-taping, biochemical tests, and computer
dietary analysis were repeated. Standards for weight
by age and weight by height were obtained from
published pediatric growth charts. 17
The indications for dietary manipulation were: (1)
intractable seizures not responding to anticonvulsant
therapy; (2) significant and long-standing concerns
about lack of weight gain; and (3) inadequate vitamin
and mineral intake to meet daily requirements. Di-
etary modifications included several modes of inter-
ventions. Methods included: (1) an increase in calorie
intake; (2) change in the caloric composition to in-
crease fat and decrease carbohydrate intake (included
ketogenic diet); and (3) vitamin and mineral supple-
mentation. The strategies employed are detailed in
Table 1.
An individual diet prescription and meal plan
was developed by the nutritionist who instructed the
caretaker, monitored implementation, and evaluated
effectiveness. Dietary changes were initiated either
on an outpatient basis or during hospitalization. Hos-
 TABLE 2
Management of Side Effects of Medium-Chain Triglyceride (MCT) Ketogenic Diet
pitalization the preferred method for the initia-
was
tion of the ketogenic diet. Implementation of the
ketogenic diet followed the procedure outlined by
Haas et al and included the use of medium-chain
triglyceride (MCT) oil.l° The distribution of calories
was as follows: 60% MCT oil, 10% other dietary fats,
10% carbohydrate, and 20% protein. The diet was in-
itiated in a three-step process beginning with a fasting
period to achieve ketosis, which was followed by feed-
ing one half of the prescribed calories, carbohydrate,
and MCT oil for approximately 24 hours; finally the
calorie intake and MCT oil was advanced as tolerated
S37
to the full diet prescription. The patients were closely the fifth percentile for weight by age and the 20th
monitored for side effects which included hypoglyce- percentile for weight by height.
mia, gas, vomiting, and diarrhea to determine how All of the patients were reported to derive great
quickly the diet could be advanced to the full pre- pleasure from food and 90% (18/21 patients) were
scription. Patients who could not tolerate the high- found to display very strong food preferences. No
calorie MCT diet were changed to a diet that reduced patient demonstrated a &dquo;poor&dquo; appetite and all but
total calories, carbohydrate, and fat. When tolerance two (10%) were evaluated as having either &dquo;good&dquo;
improved, and the patient stabilized, the diet was or &dquo;excellent&dquo; appetites. Sixteen (75%) of the total
advanced slowly to meet full prescription. Manage- population of 21 patients were unable to self-feed.
ment strategies are outlined in Table 2.18 Four of the six capable of self-feeding were stage IV
Further dietary adjustments depended on weight patients. Several of those who were able to self-feed
gain, appetite, toleration of fat, and seizure control. had reportedly gone through periods when they lost
Such modifications included alteration in prescribed the skill, only to reacquire it at a later time. Both of
calories, a reduction in total fat, change in type of fat, the two atypical patients were able to self-feed.
elimination of MCT oil, and increase in carbohydrate. The ability to chew a wide range of food textures
Alterations in the caloric composition of the diet to with no restrictions was demonstrated by 14 (66%) of
increase fat and decrease carbohydrate were accom- the 21 patients. Only two (10%) patients were found
plished by instructing the caretaker about dietary to be restricted to pureed foods and one of these
sources of fats, methods of increasing the fat content also had difficulty with thin liquids. A greater
of meals, and specific high-fat foods to be included proportion of stage III patients were limited to
daily. A moderate carbohydrate restriction was de- soft, chopped foods than of any other stage group.
fined as limiting fruit and juice to one serving daily, Seven of the eight stage IV patients could consume
avoiding other simple sugars with the exception of foods of all textures. Constipation was reported as
lactose in dairy products, and using aspartame as a a chronic complaint necessitating either dietary or

sugar substitute. laxative treatment in 71% (15/21 patients) of the total

Appropriate vitamin and mineral supplementa- population. Six of the eight stage IV patients were
tion was determined based on the Recommended constipated.
Dietary Allowances (RDAs), the patient’s nutrient The change in weight for seven patients placed
intake, and anticonvulsant therapy. Supplements on a ketogenic diet is reported in Figure 1. Weight

prescribed included multivitamins, minerals, calcium, history for 2 years prior to initiating the diet showed a
folate, iron, and zinc. 19 minimal increase, or actual weight loss, for all but one
of the subjects (patient 3). The four patients remain-
&dquo;
ing on the diet for a period of 2 years demonstrated a
Results dramatic increase in weight with one patient actually
The nutritional profile of our Rett patient population doubling her weight.
is summarized in Table 3. Of the 21 patients included Nutrient analysis of the home diet was deter-
in the study, 17 (81 % ) were below the fifth percentile mined for 15 patients and is summarized in Figure 2.
for weight by age, and 50% below the fifth percentile Caloric intake exceeded recommended energy re-
for weight by height. Ten percent had weight status quirements for age and weight with a mean intake
greater than the 50th percentile for both weight by of 98 kcal/kg.19 The caloric distribution of protein,
age and weight by height. One of the two atypical carbohydrate, and fat was appropriate for a typical
patients was above the 50th percentile for weight by American diet with 16% protein, 46% carbohydrate,
age and weight by height, and the other was below and 38% fat. The change in diet to either a ketogenic

TABLE 3
Baseline Nutritional Profile of 21 Rett Patients

P puree; S soft; Z normal; E excellent; G good; F fair; P

= = = = = = =
poor.

S38
 restriction exceeding the prescribed 10% of total
calories.
Computer analysis of the home diets indicated
common deficits in folate, zinc, vitamin D, calcium,
and iron. The ketogenic diet and high-fat diets were
found to be deficient in all vitamins and minerals
with the exception of vitamin E and essential fatty
acids.
The change in weight and dietary intake for
two patients following initiation of a high-fat, carbo-
hydrate-restricted (nonketogenic) diet is presented in
Table 4. The analysis of the home diets indicated
adequate caloric intake to meet energy requirements;
however, neither girl had gained weight during
FIGURE 1 the previous 18-month period. The high-fat, carbo-
Change in body weight during 4-year period for Rett
hydrate-restricted (nonketogenic) diet resulted in an
patients on ketogenic diet. D/C discontinued.
=

increase of 18% and 12% relative body weight for the

or high-fat diet increased calorie intake to 135 kcal/kg
and 136 kcal/kg, respectively. The distribution of
protein, carbohydrate, and fat was altered substan-
tially, representing an increase of fat from 38% of
total calories to 83% in the ketogenic diet, and 68%
in the high-fat diet. Protein intake for all diets was
adequate to meet the RDA.19 Reduction of carbo-
hydrate to 7% in the ketogenic diet represented a
FIGURE 2
Composition of diet in Rett syndrome study patients.
=
protein; CHO carbohydrate.
=
two patients studied. The change in diet increased
the total caloric intake, but more importantly the
caloric distribution was altered drastically from 28%
and 43% fat, to 66% and 71% fat, respectively. One
patient (E.E.) who gained 2.4 kg in 3 months went off
the high-fat diet for approximately 5 weeks where-
upon she lost 900 g. However, caloric intake during
this period could not be accurately assessed due to
the absence of the principal caretaker, and weight
loss may have been due to a reduction in calories
rather than a lower fat intake. The child has since
returned to the high-fat diet and is again gaining
weight. In an effort to maximize caloric intake, and
increase the MCT oil, carbohydrate-free formula has
been added to her meal plan. The second patient
(B.S.) has increased her weight by 2 kg on the high-
fat, carbohydrate-restricted nonketogenic diet. Pre-
viously, her parents had tried to promote weight gain
by feeding a high-calorie, high-carbohydrate diet,
which proved unsuccessful in initiating weight gain
even though calorie intake far exceeded recom-
mended energy requirements.
At present we have insufficient data to report
cholesterol and triglyceride values in detail. Some
initial observations include the following: (1) Several
PRO of the patients on home diets have elevated choles-
terol levels (normal 185 mg/dI20); (2) the MCT keto-

TABLE 4
Weight Status of Two Rett Patients on High-Fat Diet

CHO =
carbohydrate; Pro =
protein; DMD =
duration of modified diet.

S39
genic diet increases cholesterol or triglyceride levels
for a transitory period of approximately 6 months; (3)
the total cholesterol level increased in one patient on
a high-fat, carbohydrate-restricted diet and remained
unchanged in the other; (4) The total cholesterol-HDL
ratio for all patients irrespective of their diet was
within acceptable range, indicating no increased
cardiovascular risk. 20,21
Discussion
Many of the feeding characteristics of the Rett
population are quite distinct from other neurologic
diseases. One of the most distinguishing aspects
concerns their appetite. The
parents in our study
consistently reported good to excellent appetites
contrasting with previous reports describing these
patients as poor feeders.7,s,22 Autistic children are
similar in demonstrating good appetites, whereas the
retarded child with cerebral palsy is typically a poor
feeder with a poor appetite.13,23,24
The Rett child seems to derive great pleasure
from food, has strong food preferences, and will
become excited at the mention of a favorite food or
approaching mealtime. Many autistic children also
display strong food preferences; however, autism
has not been shown to cause the severe growth re-
tardation and malnutrition that is prevalent in Rett
syndrome. 13,23,24 The autistic child’s eating behaviors
differ from the norm in many areas and feeding prob-
lems include psychologic factors, refusal of specific
foods, and drug-nutrient interactions.23,24 However,
this does not affect their calorie intake markedly, and
hence they are not growth-weight-retarded.24
The ability to consume a variety of food textures
is variable among the Rett population. Sixty-six per-
cent of our patients were found to have no restrictions
in the type or texture of food consumed. One of the
two atypical patients was limited exclusively to
pureed foods. Several of the patients had an impaired
ability to chew and required soft or chopped foods.
Those that were capable of chewing a wide range of
foods often required great effort, and mealtimes were
lengthy. For many of these patients a change to soft,
puree textures is initiated for convenience rather than
as an expression of actual limitations. One stage III
patient recently began supplemental nasogastric feeds
to minimize feeding time and increase intake.
The impact of neurologic disease on nutritional
status is clearly recognized. Central nervous disorders
involving maxillofacial muscular function, and the
process of chewing and swallowing, affect nutrient
intake and consequently nutritional status. 13,24-26
S40
Ruby and Mathaney suggest a direct correlation be-
tween mouth area involvement and poor nutrient
intake, resulting in poor growth.26 They observed
this pattern in children with cerebral palsy .26 A cor-
relation between the severity of mental retardation
and dietary intake has been proposed by several in-
vestigators and appears to support the basis of
growth retardation observed in many neurologic
diseases. 11,12,24 The growth retardation which occurs
in cerebral palsy is a consequence of inadequate
calorie intake; however, this is clearly not the case in
Rett syndrome where adequate calorie intake has
been documented.10
Difficulty with chewing or swallowing has been
cited by some investigators as the primary reason for
inadequate calorie intake which leads to weight loss
in the Rett patient. 7,21,27 The cyclic phenomenon re-
ported by Learny28 may appear at first glance to be
applicable to the Rett population. Learny suggests that
a restriction in growth caused by a disease results in a
decreased energy requirement due to reduced muscle
mass. The decreased energy requirement causes a
reduction in appetite and caloric intake which results
in further growth reduction.28 However, our data
suggest that despite their chewing limitations and
lengthy mealtimes, these patients usually maintain
high-calorie diets. The mean caloric intake exceeds
the energy requirement established by the RDA for
age and weight.19 It appears as if good appetite
coupled with the pleasure derived from food com-
pensates for the required accommodations in texture
and feeding techniques, resulting in what would
appear to be a more than adequate calorie intake to
achieve appropriate weight.
Determination of energy requirements is difficult
among the growth-retarded and the relationship
of weight to height cannot be easily interpreted.25
Growth retardation is common in children with dis-
ordered development.24,25 It is seen in chromosomal
abnormalities and is commonly found in metabolic
disorders.29,30 Rett syndrome alters growth rate and
results in growth retardation in the majority of pa-
tients.8 Additionally, an extreme loss of muscle mass
and body weight occurs particularly in stages II and
III.3 This appears to occur irrespective of adequate
calorie intake. 10
Although hyperactive children are frequently
thin, and Rett patients demonstrate constant hand
movements, many of these girls are not ambulatory
and thus have diminished overall physical activity.
The added energy expenditure due to hand move-
ments does not seem adequate to explain the weight
loss, given their documented high calorie intake.
Ambulation has been shown to be a major factor
affecting both appetite and energy requirement in the
mentally retarded child, with the nonambulatory
group consuming significantly fewer calories than
the ambulatory group.31 The decrease in appetite is
believed to reflect the decrease in energy require-
ments. This does not appear to be true for the Rett
population many of whom are nonambulatory, yet
have excellent appetites and adequate calorie intake.
We noted in previous publications that Rett
patients demonstrated an inability to gain weight
with an adequate supply of carbohydrate calories and
that weight gain occurred when the calorie source
was changed to predominately fat. 10,32 The extended
observations reported in this paper provide further
evidence of these phenomena.
The optimal distribution of protein, carbohydrate,
and fat in the diet differs in various metabolic dis-
eases. Dietary therapy may be needed in the organic
acidemias, errors in carbohydrate metabolism, urea
acid cycle defects, and lactic acidemia.29,30 Such man-
agement may include dietary restriction of amino
acids, total protein, specific mono- and disaccharides,
or fat. If Rett syndrome is found to represent an error
in metabolism, as has been suggested, restriction of
a particular substrate with alteration in the caloric
distribution might prove helpful. Our observations
suggest this possibility.
Dietary manipulation is only advisable when
serious concerns about weight or seizure control
require it. Vitamin and mineral supplementation is
worthwhile in most patients with additional require-
ments imposed by anticonvulsant therapy. ~~ There
is no evidence that dietary therapy has any effect on
the neurologic course of Rett syndrome apart from
the improvement in seizure control experienced by
some patients maintained on a ketogenic diet. The
side effects of high-fat diets can be unpleasant, but in
our experience these problems can be overcome in
the majority of patients. With the long-term implica-
tions of a high fat intake unknown, diet modification
to a high-fat or MCT ketogenic diet should be viewed
as a temporary treatment requiring close monitoring
of serum cholesterol and triglyceride levels.
Conclusion
Although the causes of growth retardation and low
remain unclear in Rett syndrome, our data
weight
demonstrate that cachexia is a treatable complication.
We feel strongly that physicians and health care pro-
fessionals should not make the assumption that the
impaired nutritional status of the Rett patient is an
inevitableor acceptable manifestation of the disease.
Optimal development of the physical, mental, and
emotional potential for each individual depends in
part on adequate nutrition. The nutritional aspects of
Rett syndrome are important in the management of
these very vulnerable patients.
Acknowledgments
These studies were supported by a grant from the Stallone
Foundation for Autism Research and by a Clinical Research Grant
from the March of Dimes for the study of Birth Defects. R.H.H. is
supported by a Clinical Investigator Development Award from the
National Institute of Neurological and Communication Disorders
and Stroke. This project was supported in part by the University of
California San Diego General Clinical Research Center, National
Institutes of Health, Division of Research Resources grant RR00827.
References
1. Hagberg A, Aicardi J, Dias K, et al: A progressive syndrome of
autism, dementia, ataxia, and loss of purposeful hand use in
girls: Rett’s syndrome: Report of 35 cases. Ann Neurol 1983;14:
471-479.
2. Hagberg A, Goutieres F, Hanefeld F, et al: Rett syndrome:
Criteria for inclusion and exclusion. Brain Dev 1985;7:372-373.
3. Naidu S, Murphy M, Moser H, et al: Rett syndrome—natural
history in 70 cases. AmMed Genet 1986;24(suppl 1):61-72.
4. Philippart M: Clinical recognition of Rett syndrome. Arrt J Med
Genet 1986;24(suppl 1):111-118.
5. Hagberg B, Witt-Engerström I: Rett syndrome: A suggested
staging system for describing impairment profile with increas-
ing age towards adolescence. AmJ Med Genet 1986;24(suppl
1):47-59.
6. Rett A: Über ein zerebral-atrophisches Syndrom bei Hyperam-
moniämie. Vienna, Bruder Hollinek, 1966.
7. Budden S: Rett syndrome: Studies of 13 affected girls. Am J
Med Genet 1986;24(suppl 1):99-110.
8. Holm VA: Physical growth and development in patients with
Rett syndrome. Am J Med Genet 1986;24(suppl 1):119-126.
9. Misslvietz J, Depastas G: Forensic problems in Rett syndrome.
Brain Dev 1985;7:326-328.
10. Haas RH, Rice MLA, Trauner DA, et al: Therapeutic effects of a
ketogenic diet in Rett syndrome. AmJ Med Genet 1986;24(suppl
1):225-246.
11. Garn S, Weir HF: Assessing the nutritional status of the
mentally retarded. AmJ Clin Nutr 1971;24:853-857.
12. Palmer S: Nutrition and developmental disorders, an overview,
in Palmer S, Ervall S (eds): Pediatric Nutrition in Developmental
Disorders. Springfield, III, Charles C Thomas, 1978, pp 21-24.
13. Howard RB: Nutritional support of the developmentally dis-
abled child, in Suskind RM (ed): Textbook of Pediatric Nutrition.
New York, Raven Press, 1981, pp 577-582.
14. Goutieres F, Aicardi J: Atypical forms of Rett syndrome. Am J
Med Genet 1986;24(suppl 1):183-194.
15. Hagberg B, Rasmussen P: "Forme fruste" of Rett syndrome—
a case report. Am J Med Genet 1986;24(suppl 1):175-182.
16. Nutritionist III, Silverton, Ore, N-squared Computing, 1980.
17. NCHS Growth Percentiles. Columbus, Ohio, Ross Laboratories,
1980. [Adapted from Hamill PVV, Drizd TA, Johnson CL, et al:
Physical growth: National Center for Health Statistics per-
S41
 centiles. AmClin Nutr 1979;32:607-629.]
18. Gwynne J, Rice MLA: The MCT-Ketogenic Diet Handbook. A
Resource Guide for the Health Professional, in press. [Will be avail-
able from the authors: 2670 Del Mar Heights Rd. #127, Del
Mar, CA 92014.]
19. Recommended Dietary Allowances, ed 9. Washington DC,
National Academy of Sciences, 1980.
20. The Expert Panel: Report of the national cholesterol education
program expert panel on detection, evaluation and treatment
of high blood cholesterol in adults. Arch Intern Med 1988;
148:36-69.
21. Epidemiology Committee Lipid Research Clinics Program:
Plasma lipid distributions in selected North American popula-
tions : The Lipid Research Clinics Program Prevalence Study.
Circulation 1979;60:427-436.
22. Hanks SB: The role of therapy in Rett syndrome. Am J Med
Genet 1986;24(suppl 1):247-252.
23. Raiten DJ, Massaro T: Perspectives on the nutritional ecology
of autistic children. J Autism Dev Disord 1986;16:133-145.
24. American Dietetic Association House of Delegates: Position of
the American Dietetic Association: Nutrition in comprehensive
program planning for persons with developmental disabilities:
S42
Technical support paper. J Am Diet Assoc 1987;87:1068-1074.
25. Wodarski LA: Nutrition intervention in developmental dis-
abilities : An interdisciplinary approach. J Am Diet Assoc
1985;85:218-221.
26. Ruby DO, Mathany WD: Comments on growth of cerebral-
palsied children.J Am Diet Assoc 1962;40:525-528.
27. Olsson B, Rett A: Behavioral observations concerning differen-
tial diagnosis between the Rett syndrome and autism. Brain
Dev 1985;7:281-289.
28. LearnyCM: A study of the food intake of a group of children
with cerebral palsy in the Lakeville Sanitorium. AmJ Public
Health 1953;43:1310-1316.
29. Nyhan WL, Sakati NO: Diagnostic Recognition of Genetic Disease.
Philadelphia, Lea & Febiger, 1987.
30. Nyhan WL: Abnormalities of Amino Acid Metabolism in Clinical
Medicine. East Norwalk, Conn, Appleton-Century-Crofts, 1984.
31. Culley WJ, Middleton TO: Caloric requirements of mentally
retarded children with and without motor dysfunction.J
Pediatr, 1969;75:380-384.
32. Haas R, Rice MLA: Is Rett’s syndrome a disorder of carbohy-
drate metabolism? Hyperpyruvic acidemia and treatment by
ketogenic diet. Ann Neurol 1985;18:418.