Acta Paediatr 81: 686-90. 1992
Growth and nutrition in 10 girls with Rett syndrome M Thommessen, BF Kase and A Heiberg Institule for Nutrition Research, School of Medicine. University of Oslo. Department of Pediatric Research, The National Hospital. Oslo and Frambu Health Centre, Siggerud, Norway
Thommessen M, Kase BF, Heiberg A. Growth and nutrition in 10 girls with Rett syndrome. Acta Prediatr 1992;81:686-90. Stockholm. ISSN 0803-5253 Cross-sectional and retrospective data on growth and anthropometric outcome, feeding problems and dietary intake are presented for 10 girls between three and 16 years of age with Rett syndrome. All girls had birth weight and length within the normal range for gestational age and development was considered normal until six to 24 mooths of age. The girls presented a fall off in linear growth during the first two years of life and at the time of study, all but one had height and/or weight for height below the 2.5th percentile of healthy children. The girls had good appetite but could not eat by themselves and oral-motor dysfunctions were common. The mean energy intake was 66.9% of the US recommendations according to age and 107.8% of the recommendations according to body weight. The intakes of thiamin, vitamin D, calcium and iron were considered low. None was anaemic. Different nutritional intervention strategies should be investigated to reduce and, if possible, prevent malnutrition and wasting in girls with Rett syndrome. 0 Feeding problems, growth, nutrition, Rett syndrome M Thommessen, Oslo City Department of Environmental Health, St. Olavsplass 5,0165 Oslo I, Norway
Rett syndrome, a progressive neurological disorder was first reported by Andreas Rett in 1966. Since 1983, a series of reports on its clinical entity and prevalence has provided international recognition for Rett syndrome (1-6). The inherited condition affects only girls and is characterized by progressive psychomotor retardation, ataxia, microcephaly, seizures, dementia, autistic behavior and development of stereotypic hand movements (“hand-washing”). The patients appear normal at birth and during the first months of life, until the first nonspecific signs of developmental stagnation appear between six and 18 months of age (7). The subsequent deteriorative development of the syndrome has been described in four stages by Hagberg & Witt-Engerstrom (8). The etiology of Rett syndrome is still unknown and without biological markers (7). Following the international recognition of the syndrome, several reports have added the presence of growth retardation, feeding and nutritional problems to the list of clinical findings in girls with Rett syndrome (9-1 5). The aims of this study were to investigate growth and dietary intake in 10 Norwegian girls with Rett syndrome and to discuss the relative importance of feeding problems on growth and daily care of these patients.
girls and their parents attended a two-week course for families with mentally retarded children at Frambu Health Centre, an information and treatment center for families with disabled children (16). All patients were living and cared for at home at the time of study. All girls fulfilled the criteria of classic Rett syndrome (17), with the possible exception of patient no. 1, who was diagnosed at four years of age on the basis of progressive deterioration from 10 months of age. She, as well as the others, were seen by B Hagberg, Sweden, during their stay at Frambu Health Center. All girls were assessed according to the four clinical stages in Rett syndrome (8) (Table I). Four girls were able to walk slowly with assistance at the time of study, but wheelchairs or pushchairs were usually used.
Material and methods
Growthfrom birth Records on height and weight from birth were collected from the Mother-and-Child Health Centers where the girls had been followed. For two girls, records were obtained up to four years of age, for seven up to two years of age and for one girl the growth record covered only the first year of life. For two girls born five and six weeks before term, no growth data after birth were available. Information concerning gestational age was missing for two girls, while the other six girls were born at term.
The study included nine Norwegian girls and one girl of Philipine origin (patient no. 1) between 3.8 and 16.2 years of age (Table I). The data were collected while the
Anthropometric and biochemical assessment Height and weight, triceps skinfold thickness (TSF),
Table I . Age, stage of Rett syndrome according to Hagberg & WittEngerstrom (8) and main additional clinical features in 10 girls with Rett syndrome.
Patient no.
I 2 3 4 5 6 7
a
9 10
Age (years) 6.4 6.8 3.8 10.4 10.0 4.1 7.2 11.1 6.0 16.2
687
Growth and nutrition in Rett syndrome
ACTA PiEDIATR 81 (1992)
Stage*
Ill Ill Ill Ill 111 111
Ill IV I11 IV
I
A130
Main clinical features Epilepsy Epilepsy Epilepsy Scoliosis Epilepsy Epilepsy Epilepsy, scoliosis Scoliosis Epilepsy? Epilepsy, scoliosis
* Stage Ill = “Pseudostationary stage” characterized by apraxia, washing stereotypes of the hands and jerky truncal ataxia. Motor ability preserved and communication improved. Stage IV = “Late motor deteriorationstage” characterized by severe motor impairment and non-ambulance. upper-arm circumference (UAC) and arm-muscle circumference (AMC) were measured as anthropometric indicators of nutritional state at the time of study. For each girl, height and weight were converted to relative values as percentages of the average height for age and weight for height of healthy girls (18). The method is described in detail elsewhere (19). Relative height at 93% and relative weight for height at 85% correspond to the 2.5th percentiles of the standard growth charts. TSF and UAC were measured on the left arm (20). The AMC was calculated from the TSF and UAC using the formula: AMC=UAC-3.14*TSF (21). The arm measurements are presented as percentages of the corresponding means for age of TSF, UAC and AMC derived from healthy American boys and girls (22). For two girls, reliable measures for weight and UAC were not obtained. Venous blood samples were analyzed for hemoglobin (Hb), hematocrit (HCT), serum ferritin and serum folate by standard methods at the Department of Clinical Chemistry, National Hospital, Oslo. Girls with Hb < 1 1.O g/dl were considered anemic, while serum ferritin values below the laboratory reference range of 11-210 ug/l, indicated depleted iron stores. The reference range of serum folate was 6-20 mmol/l. Evaluation of motorfeeding problems at the time of study Self-feeding skills and oral-motor function (chewing and swallowing) were assessed by the physiotherapists and occupational therapists at Frambu Health Centre (1 9). All had impaired self-feeding skills and oral-motor dysfunction at the time of study. hterview with the parents and dietary intake assessment All parents were interviewed according to a semi-
441 ‘ 1 1 1 1 1 0 1 2 3 4 5 6
months
I 9
I
12
I 18 Age
I 2
I 3
4
5
6
years
Fig. 1. Growth from birth in eight girls with Rett syndrome. Height according to the 97.5th, 50th and 2.5th percentiles of healthy
Norwegian girls (18).
structured guide (23) on dietary habits, feeding practice and feeding problems from birth until the time of study. Information concerning feeding practice at home (e.g. whether the girls were self-feeding or assisted), and information concerning food texture at the time of study were also collected from these interviews. In addition, all parents were asked to complete a fourday estimated record of their daughter’s food intake at home (24). The parents were carefully taught how to keep the record through oral and written instructions (25). The parents of seven girls responded to this part of the study. For each girl, the daily intake of energy and nutrients were calculated as percentages of the US Average Energy Allowances for age and kg body weight for healthy children and of the US Recommended Dietary Allowances (RDAs) for different nutrients (26).
Results Growthfrom birth and outcome at the time of study
Birth length ranged from 46 to 51 cm and birth weight from 2.5 to 4.1 kg. Length and weight at birth were within the normal range according to gestational age (2.5th-97.5th percentile) for all the girls. The individual growth curves of eight girls are presented in Figs. 1 and 2. As the girls became older, height and weight gradually decreased relative to the average for healthy girls and at two years of age three girls had height and/or weight below the 2.5th percentile. Growth outcome at the time of study showed a
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markedly reduced height for age and/or weight for height in all but one girl. Seven girls were growth retarded with height for age below 93% of the average for healthy children (percentage corresponding to the 2.5th percentile), and six children were underweight with weight for height below 85% (percentage corresponding to the 2.5th percentile). Four girls (patients nos 3, 4, 5 and 10) had UAC and AMC below the 5th percentile and five girls (patients nos 2, 5 , 7, 9, 10) had subnormal values of TSF (Table 2). The mean (SD) Hb, HCT and serum ferritin were 13.1 (0.8) g/dl, 39.2 (14.2) % and 22.9 (14.2) pg/l, respectively. None of the girls was anemic, but two girls (patients nos 3 and 10) had serum ferritin levels less than . 1 1 pg/l. The mean (SD) serum folate concentration was 13.2 (6.3) mmol/l. Patient no. 10 had serum folate levels below the reference range.
-4
-3
21 0
'
1
I 2
I I l l 3 4 5 6 Age. months
I
I
9
12
1 12 1 8 2 4
Fig. 2. Growth from birth in eight girls with Rett syndrome. Weight
according to the 97.5th, 50th and 2.5th percentiles of healthy Norwegian girls (18).
Table 2. Relative height, weight for height, upper-arm circumference (UAC), arm-muscle circumference (AMC) and triceps skinfold thickness (TSF) in 10 girls with Rett syndrome. All values in %. Patient no. I 2 3 4 5 6 7 8 9 10
Height
Weight
UAC
AMC
TSF
92.5 89.3 96.6 88.7 77.9 99.5 88.3 93.8 83.8 77.4
110.7 87.6 80.6 83.0 65.7 82.4 74.5 91.2 75.3
98.3 90.4 88.7 81.9 64.5 94.8 90.9 86.7 83.3
101.3 96.1 93.8 86.4 71.0 102.0
80.0 55.0 63.0 58.3 33.3 60.0 30.0 75.0 57.0 58.3
-
-
93.8 92.4 88.1
Table 3. Nutrient intake in seven girls with Rett syndrome. Means (SD) calculated as percentages of the US Recommended Dietary Allowances for healthy children (26). Relative intake Nutrient Vitamin A Vitamin D Vitamin C Thiamin Riboflavin Calcium Iron
(%)
114.3 (52.9) 14.2 (7.7) 107.8 (63.4) 59.8 (10.4) 87.0 (22.7) 72.1 (13.8) 57.1 (10.5)
Early feeding habits and development All parents reported normal feeding behavior with regard to sucking, breast feeding, weaning and transition to solid food during the first year of life. The appetite was described as good in all but one girl. However, two girls (patients nos 6 and 7) failed to follow normal feeding development after one year of age. One became anorectic and the other stopped eating solid food. Discontinuation in normal eating development was reported for another two girls (patients nos 2 and 3) from 18 months, for patient no. 10 from three years and for patient no. 5 from eight years of age. At the time of study, all girls were assisted during meals. Five girls were fed with pureed food only, four with both solid and pureed food and only one girl (patient no. 1) ate regular solid food (bread slices, dinner in pieces). Energy and nutrient intake at the time of study The mean (SD) relative energy intakes in the seven girls for whom dietary data were obtained were 66.9 (1 5.6) % of the Average Energy Allowances for age, and 107.8 (15.9) % of the allowances per kg body weight. Comparison of dietary and anthropometric data showed a good correlation between relative energy intake for age and relative height and weight. Three girls (patients nos 5, 8 and 10) had energy intakes below 70% of the average allowances for age. The mean (SD) intake of protein was 40.0 (6.8) g/day. Caloric composition of home diets showed that protein contributed 10-16%, fat 1 6 4 % and carbohydrates 45-71 YOof daily energy intakes. With the exception of vitamin A and C, the mean intakes of nutrients in the registration period were generally low (Table 3). Intakes of nutrients below 70% of the RDAs were most frequent for vitamin D (all), thiamin (five) and iron (six). Low intake of the different nutrients did not follow energy intake specifically.
ACTA PEDIATR 81 (1992)
Discussion When this study was undertaken (1987) 20 girls with Rett syndrome were identified in Norway. Prevalence figures for Rett syndrome in Sweden indicate a frequency of one case per 12-13000 girls (27). Girls with Rett syndrome constitute a small, but severely disabled group of handicapped children, whose demand for care and support increases with age. Growth retardation, feeding and nutritional problems are only some of the features that girls with Rett syndrome exhibit. In this study of 10 girls with Rett syndrome we found that growth retardation, underweight, reduced muscle mass and depleted energy stores were frequent. Two children failed to gain height and/or weight at the expected rate from 3-6 months of age, one from one year of age and four after two years of age. According to the parents, developmental delay was first suspected at a median age of one year (range from six months to two years of age). In 1986 physical growth was reported in 21 girls with Rett syndrome (12). In this study abnormal growth development was found in 18 (86%) of the patients, with 10 girls having linear growth below the 5th percentile of healthy children and eight girls exhibiting a fall off in growth during the first 1-4 years of life. From her study, Holm proposed that growth retardation and early fall off in expected growth could be useful markers in Rett syndrome (12). The results from our study revealed that the growth retardation had started after the parents had begun to suspect that “something was wrong” with the child, and in five of the cases, after the onset of the first feeding problems. Thus, relative to growth retardation, feeding problems and failure to follow normal feeding development may be an even earlier marker. Neither growth retardation nor feeding problems are, however, specific for Rett syndrome alone (19). In addition, our, as well as other case reports have shown that there are exceptions, namely girls who grow at the expected rate and even appear stubby (4). The diagnosis of Rett syndrome is usually tentative until stage I1 develops by 1-3 years of age (7, 27). The cause of growth retardation, as well as the etiology of Rett syndrome itself, are still unknown. Growth retardation is generally described as an inherent part of the progressive deterioration of higher brain functions and the resulting neurological abnormalities. Studies have not yet revealed significant explanations from metabolic disorders (28), intestinal dysfunctions or malabsorption symptomatology (29). As a consequence of the stereotypic hand movements and incessant hand-to-mouth movements, most girls with Rett syndrome develop oral-motor dysfunctions and poor self-feeding abilities (5, 9, 10, 13-15). In a previous report on the energy intake in disabled children, we found that children who have oral-motor dysfunctions and impaired self-feeding skills eat less compared to (allowances for age) their disabled counter-
Growth and nutrition in Rett syndrome
689
parts without feeding problems (25). In spite of good appetite, it may thus be proposed that reduced food intake is a contributing factor to growth retardation and wasting in girls with Rett syndrome due to longstanding mechanical feeding problems. All the patients for whom dietary records were obtained had energy intakes considerably below‘the mean allowance for age of healthy children. The evaluation of energy requirement for disabled children is difficult. Children with spasms and frequent involuntary movements may have relatively increased energy consumption, while the energy consumption in non-ambulatory children may be relatively decreased compared to healthy children (30). Increased energy rkquirement is also present in children who are going to catch-up previous growth retardation and wasting. The energy intake is calculated per kg body weight. In studies by Haas and colleagues (1 1 ,31,32), as well as in the present study, the girls had energy intakes per kg body weight above the allowances for healthy children. Haas and colleagues pinpointed the paradox that the patients were malnourished in spite of an above normal caloric intake. In their studies they have shown that girls with Rett syndrome may gain substantial weight on high energy, ketogenic diets, but it is still open to question whether the positive results can be ascribed to high fat content per se or to an increased total caloric intake. Taking into account that the girls have abnormally low weight, it is our opinion that the high energy intakes per kg body weight are “falsely” elevated compared to the allowances per kg body weight of healthy children. Thus, to compensate for growth retardation and lack of weight maintenance, we believe that the patients should be provided with substantially more calories than recommended for healthy children. In our study one girl was put on a diet without gluten after she was diagnosed autistic. According to the parents, the diet neither improved the growth nor the development of the child after one year. Another girl (patient no. 6) received a diet free from both gluten and lactose a t the time of study, but after a year and a half no clinical improvement was observed. Feeding problems in girls with Rett syndrome are of primary concern to parents and therapists (14). Several studies have demonstrated positive results with regard to improvement of mobility and posture and reduction of hand wringing and hand-to-mouth movements (1 0, 33-35). In a single case study, Sharpe & Ottenbacher (35) found a modest improvement in the amount of cereal consumed and in the time required to eat by use of elbow restraint. The therapy programs have made feeding easier for the parents (33). Stewart et al. (14) have suggested stage 111 of Rett syndrome as the best period for facilitating new motor skills, while every effort should be made to minimize the loss of functional skills during stages I1 and IV of the syndrome. We conclude that feeding problems and inadequate intake of energy and nutrients are likely to be contribut-
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ing causes of lack of weight maintenance and poor growth in girls with Rett syndrome. Different nutritional intervention and therapy strategies such as increased number of meals per day, night meals (1 3), feeding of high-energy, high-fat diets (1 1, 3 1-32), vitamin and energy supplementation, tube feeding and gastrostomy (1 0) should be considered individually. Acknow/edgements.-This study was supported by the Norwegian Research Council for Science and the Humanities, and the Norwegian Research Council for Applied Social Science. The work was finished during employment at the Oslo Department of Environmental Health. The authors also gratefully acknowledge nutritionists Hege Araldsen, Jorunn Gran-Henriksen and h e Borgejordet for their help during data collection and the staff at Frambu Health Center, and the children and the parents for cooperation during the study.
References I . Haberg B, Aicardi J, Dias K, Ramos 0. 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;14471-9 2. Hagberg B. Rett’s syndrome: Prevalence and impact on progressive severe mental retardation in girls. Acta Paediatr Scand 1985;74:405-8 3. Rolando S. Rett syndrome: Report of eight cases. Brain Dev 1985;7:290-6 4. Adkins WN. Rett syndrome at an institution for the developmentally disabled. Am J Med Genet 1986;24:85-97 5 . Budden SS. Rett syndrome: Studies of 13 affected girls. Am J Med Genet 1986;24:99-109 6. Bostad R, Kiil R. Rett syndrome. Et nytt sykdomsbilde. Tidsskr Nor Laegeforen 1987;107:1659-6 1 7. Hagberg B. Rett syndrome: Clinical pecularities, diagnostic approach, and possible cause. Review article. Pediatr Neurol 1989;5:75-83 8. Hagberg B, Witt-Engerstrom 1. Rett syndrome: A suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet 1986;24:47-59 9. Olsson B, Rett A. Behavioural observations concerning differential diagnosis between the Rett syndrome and autism. Brain Dev 1985;7:281-9 10. Hanks SB. The role of therapy in Rett syndrome. Am J Med Genet 1986;24247-52 1 I. Haas RH, Rice MA, Trauner DA, Merritt TA. Therapeutic effects of a ketogenic diet in Rett syndrome. Am J Med Genet I986;24:225-46 12. Holm VA. Physical growth and development in patients with Rett syndrome. Am J Med Genet 1986;24:119-26 13. Murphy M. Day to day care of Rett syndrome children. Brain Dev 1987;9:546-9 14. Stewart KB, Brady DK, Crowe TK, Naganuma GM. Rett syndrome: A literature review and survey of parents and therapists. Phys Occup Ther Pediatr 1989;9:35-55 15. Budden S, Meek M. Henighan C. Communication and oral-
ACTA PEDIATR 81 (1992)
motor function in Rett syndrome. Dev Med Child Neurol 1990;32:51-5 16. Storhaug K, Vandvik IH. Frambu Health Centre: Promoting family focused care for disabled children. Int J Rehabil Res 1983;6:175-82 17. Hagberg B, Goutieres F, Hanefeld F, Rett A, Wilson J. Rett syndrome: Criteria for inclusion and exclusion. Brain. Dev 1985;7:372-3 18. Knudtzon J, Waaler PE, Skjerven R, Solberg LK, Steen J. Nye vekstkurver for Norske barn. Tidsskr Nor Lzgeforen 1988;108: 2125-35 19. Thommessen M, Heiberg A, Kase BF, Larsen S , Riis G. Feeding problems, height and weight in different groups of disabled children. Acta Paediatr Scand 1991;80:527-33 20. Merritt RJ, Blackburn GL. Nutritional assessment and metabolic response to illness of the hospitalized child. In: Suskind RM ed Textbook of Pediatric Nutrition. New York: Raven Press, 1981 21. Gray GE, Gray LK. Anthropometric measurements and their interpretations: Principles, practices and problems. J Am Diet ASSOC1980;77:534-9 22. Frisancho AR. Triceps skinfold and upper arm muscle size, norms for assessment of nutritional status of the United States population. Am J Clin Nutr 1974;27:1052-8 23. Lofland J, Lofland LH. Analyzing Social Settings. A Guide to Qualitative Observation and Analysis 2nd Edn. Belmont: Wadswort Publishing Comp, 1984 24. Nelson M. Estimated records. In: Cameron ME, Van Staveren WA eds Manual on Methodology for Food Consumption Studies. Oxford: Oxford University Press, 1988:M-75 25. Thommessen M, Riis G, Kase BF, Larsen S, Heiberg A. Energy and nutrient intakes in disabled children with and without feeding problems. J Am Diet Assoc, in press 26. Food and Nutrition Board. Recommended dietary allowances 10th Edn. Washington DC: National Academy of SciencesNational Research Council, 1989 27. Witt-Engerstrom I. Rett syndrome in Sweden. Neurodevelopment, disability, phatophysiology. Goteborg: Goteborgs Universitet, 1990 Dissertation 28. Vles JSH, Spaapen LJM, Schrander-Stumpel C, van der Meer S. Metabolic investigation of a patient with Rett syndrome. Eur J Pediatr 1989;148:786 29. Hagberg B, Witt-Engerstrom I. Rett syndrome: Epidemiology and nosology. Progress in knowledge 1986.A conference communication. Brain Dev 1987;9:451-7 30. Culley WJ, Middleton TO. Caloric requirements of mentally retarded children with and without motor dysfunction. J Pediatr 1969;75:380-4 3 I , Rice MA, Haas RH. The nutritional aspects of Rett syndrome. J Child Neurol 1988; (Suppl 3): 35-42 32. Haas RH, Rice MA. Nutrition in the Rett syndrome: Report of ongoing studies. Brain Dev 1990; I2:49 33. Aron M. The use and effectiveness of elbow splints in the Rett syndrome. Brain Dev 1990;12:162-3 34. Hanks SB. Motor disabilities in the Rett syndrome and physical therapy strategies. Brain Dev 1990;12:157-61 35. Sharpe PA, Ottenbacher KJ. Use of an elbow restraint to improve finger-feeding skills in a child with Rett syndrome. Am J Occup Ther 1990;44:328-32 Received Feb. 19, 1991. Accepted Sep. 12, 1991
Growth and nutrition in 10 girls with Rett syndrome M Thommessen, BF Kase and A Heiberg Institule for Nutrition Research, School of Medicine. University of Oslo. Department of Pediatric Research, The National Hospital. Oslo and Frambu Health Centre, Siggerud, Norway
Thommessen M, Kase BF, Heiberg A. Growth and nutrition in 10 girls with Rett syndrome. Acta Prediatr 1992;81:686-90. Stockholm. ISSN 0803-5253 Cross-sectional and retrospective data on growth and anthropometric outcome, feeding problems and dietary intake are presented for 10 girls between three and 16 years of age with Rett syndrome. All girls had birth weight and length within the normal range for gestational age and development was considered normal until six to 24 mooths of age. The girls presented a fall off in linear growth during the first two years of life and at the time of study, all but one had height and/or weight for height below the 2.5th percentile of healthy children. The girls had good appetite but could not eat by themselves and oral-motor dysfunctions were common. The mean energy intake was 66.9% of the US recommendations according to age and 107.8% of the recommendations according to body weight. The intakes of thiamin, vitamin D, calcium and iron were considered low. None was anaemic. Different nutritional intervention strategies should be investigated to reduce and, if possible, prevent malnutrition and wasting in girls with Rett syndrome. 0 Feeding problems, growth, nutrition, Rett syndrome M Thommessen, Oslo City Department of Environmental Health, St. Olavsplass 5,0165 Oslo I, Norway
Rett syndrome, a progressive neurological disorder was first reported by Andreas Rett in 1966. Since 1983, a series of reports on its clinical entity and prevalence has provided international recognition for Rett syndrome (1-6). The inherited condition affects only girls and is characterized by progressive psychomotor retardation, ataxia, microcephaly, seizures, dementia, autistic behavior and development of stereotypic hand movements (“hand-washing”). The patients appear normal at birth and during the first months of life, until the first nonspecific signs of developmental stagnation appear between six and 18 months of age (7). The subsequent deteriorative development of the syndrome has been described in four stages by Hagberg & Witt-Engerstrom (8). The etiology of Rett syndrome is still unknown and without biological markers (7). Following the international recognition of the syndrome, several reports have added the presence of growth retardation, feeding and nutritional problems to the list of clinical findings in girls with Rett syndrome (9-1 5). The aims of this study were to investigate growth and dietary intake in 10 Norwegian girls with Rett syndrome and to discuss the relative importance of feeding problems on growth and daily care of these patients.
girls and their parents attended a two-week course for families with mentally retarded children at Frambu Health Centre, an information and treatment center for families with disabled children (16). All patients were living and cared for at home at the time of study. All girls fulfilled the criteria of classic Rett syndrome (17), with the possible exception of patient no. 1, who was diagnosed at four years of age on the basis of progressive deterioration from 10 months of age. She, as well as the others, were seen by B Hagberg, Sweden, during their stay at Frambu Health Center. All girls were assessed according to the four clinical stages in Rett syndrome (8) (Table I). Four girls were able to walk slowly with assistance at the time of study, but wheelchairs or pushchairs were usually used.
Material and methods
Growthfrom birth Records on height and weight from birth were collected from the Mother-and-Child Health Centers where the girls had been followed. For two girls, records were obtained up to four years of age, for seven up to two years of age and for one girl the growth record covered only the first year of life. For two girls born five and six weeks before term, no growth data after birth were available. Information concerning gestational age was missing for two girls, while the other six girls were born at term.
The study included nine Norwegian girls and one girl of Philipine origin (patient no. 1) between 3.8 and 16.2 years of age (Table I). The data were collected while the
Anthropometric and biochemical assessment Height and weight, triceps skinfold thickness (TSF),
Table I . Age, stage of Rett syndrome according to Hagberg & WittEngerstrom (8) and main additional clinical features in 10 girls with Rett syndrome.
Patient no.
I 2 3 4 5 6 7
a
9 10
Age (years) 6.4 6.8 3.8 10.4 10.0 4.1 7.2 11.1 6.0 16.2
687
Growth and nutrition in Rett syndrome
ACTA PiEDIATR 81 (1992)
Stage*
Ill Ill Ill Ill 111 111
Ill IV I11 IV
I
A130
Main clinical features Epilepsy Epilepsy Epilepsy Scoliosis Epilepsy Epilepsy Epilepsy, scoliosis Scoliosis Epilepsy? Epilepsy, scoliosis
* Stage Ill = “Pseudostationary stage” characterized by apraxia, washing stereotypes of the hands and jerky truncal ataxia. Motor ability preserved and communication improved. Stage IV = “Late motor deteriorationstage” characterized by severe motor impairment and non-ambulance. upper-arm circumference (UAC) and arm-muscle circumference (AMC) were measured as anthropometric indicators of nutritional state at the time of study. For each girl, height and weight were converted to relative values as percentages of the average height for age and weight for height of healthy girls (18). The method is described in detail elsewhere (19). Relative height at 93% and relative weight for height at 85% correspond to the 2.5th percentiles of the standard growth charts. TSF and UAC were measured on the left arm (20). The AMC was calculated from the TSF and UAC using the formula: AMC=UAC-3.14*TSF (21). The arm measurements are presented as percentages of the corresponding means for age of TSF, UAC and AMC derived from healthy American boys and girls (22). For two girls, reliable measures for weight and UAC were not obtained. Venous blood samples were analyzed for hemoglobin (Hb), hematocrit (HCT), serum ferritin and serum folate by standard methods at the Department of Clinical Chemistry, National Hospital, Oslo. Girls with Hb < 1 1.O g/dl were considered anemic, while serum ferritin values below the laboratory reference range of 11-210 ug/l, indicated depleted iron stores. The reference range of serum folate was 6-20 mmol/l. Evaluation of motorfeeding problems at the time of study Self-feeding skills and oral-motor function (chewing and swallowing) were assessed by the physiotherapists and occupational therapists at Frambu Health Centre (1 9). All had impaired self-feeding skills and oral-motor dysfunction at the time of study. hterview with the parents and dietary intake assessment All parents were interviewed according to a semi-
441 ‘ 1 1 1 1 1 0 1 2 3 4 5 6
months
I 9
I
12
I 18 Age
I 2
I 3
4
5
6
years
Fig. 1. Growth from birth in eight girls with Rett syndrome. Height according to the 97.5th, 50th and 2.5th percentiles of healthy
Norwegian girls (18).
structured guide (23) on dietary habits, feeding practice and feeding problems from birth until the time of study. Information concerning feeding practice at home (e.g. whether the girls were self-feeding or assisted), and information concerning food texture at the time of study were also collected from these interviews. In addition, all parents were asked to complete a fourday estimated record of their daughter’s food intake at home (24). The parents were carefully taught how to keep the record through oral and written instructions (25). The parents of seven girls responded to this part of the study. For each girl, the daily intake of energy and nutrients were calculated as percentages of the US Average Energy Allowances for age and kg body weight for healthy children and of the US Recommended Dietary Allowances (RDAs) for different nutrients (26).
Results Growthfrom birth and outcome at the time of study
Birth length ranged from 46 to 51 cm and birth weight from 2.5 to 4.1 kg. Length and weight at birth were within the normal range according to gestational age (2.5th-97.5th percentile) for all the girls. The individual growth curves of eight girls are presented in Figs. 1 and 2. As the girls became older, height and weight gradually decreased relative to the average for healthy girls and at two years of age three girls had height and/or weight below the 2.5th percentile. Growth outcome at the time of study showed a
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markedly reduced height for age and/or weight for height in all but one girl. Seven girls were growth retarded with height for age below 93% of the average for healthy children (percentage corresponding to the 2.5th percentile), and six children were underweight with weight for height below 85% (percentage corresponding to the 2.5th percentile). Four girls (patients nos 3, 4, 5 and 10) had UAC and AMC below the 5th percentile and five girls (patients nos 2, 5 , 7, 9, 10) had subnormal values of TSF (Table 2). The mean (SD) Hb, HCT and serum ferritin were 13.1 (0.8) g/dl, 39.2 (14.2) % and 22.9 (14.2) pg/l, respectively. None of the girls was anemic, but two girls (patients nos 3 and 10) had serum ferritin levels less than . 1 1 pg/l. The mean (SD) serum folate concentration was 13.2 (6.3) mmol/l. Patient no. 10 had serum folate levels below the reference range.
-4
-3
21 0
'
1
I 2
I I l l 3 4 5 6 Age. months
I
I
9
12
1 12 1 8 2 4
Fig. 2. Growth from birth in eight girls with Rett syndrome. Weight
according to the 97.5th, 50th and 2.5th percentiles of healthy Norwegian girls (18).
Table 2. Relative height, weight for height, upper-arm circumference (UAC), arm-muscle circumference (AMC) and triceps skinfold thickness (TSF) in 10 girls with Rett syndrome. All values in %. Patient no. I 2 3 4 5 6 7 8 9 10
Height
Weight
UAC
AMC
TSF
92.5 89.3 96.6 88.7 77.9 99.5 88.3 93.8 83.8 77.4
110.7 87.6 80.6 83.0 65.7 82.4 74.5 91.2 75.3
98.3 90.4 88.7 81.9 64.5 94.8 90.9 86.7 83.3
101.3 96.1 93.8 86.4 71.0 102.0
80.0 55.0 63.0 58.3 33.3 60.0 30.0 75.0 57.0 58.3
-
-
93.8 92.4 88.1
Table 3. Nutrient intake in seven girls with Rett syndrome. Means (SD) calculated as percentages of the US Recommended Dietary Allowances for healthy children (26). Relative intake Nutrient Vitamin A Vitamin D Vitamin C Thiamin Riboflavin Calcium Iron
(%)
114.3 (52.9) 14.2 (7.7) 107.8 (63.4) 59.8 (10.4) 87.0 (22.7) 72.1 (13.8) 57.1 (10.5)
Early feeding habits and development All parents reported normal feeding behavior with regard to sucking, breast feeding, weaning and transition to solid food during the first year of life. The appetite was described as good in all but one girl. However, two girls (patients nos 6 and 7) failed to follow normal feeding development after one year of age. One became anorectic and the other stopped eating solid food. Discontinuation in normal eating development was reported for another two girls (patients nos 2 and 3) from 18 months, for patient no. 10 from three years and for patient no. 5 from eight years of age. At the time of study, all girls were assisted during meals. Five girls were fed with pureed food only, four with both solid and pureed food and only one girl (patient no. 1) ate regular solid food (bread slices, dinner in pieces). Energy and nutrient intake at the time of study The mean (SD) relative energy intakes in the seven girls for whom dietary data were obtained were 66.9 (1 5.6) % of the Average Energy Allowances for age, and 107.8 (15.9) % of the allowances per kg body weight. Comparison of dietary and anthropometric data showed a good correlation between relative energy intake for age and relative height and weight. Three girls (patients nos 5, 8 and 10) had energy intakes below 70% of the average allowances for age. The mean (SD) intake of protein was 40.0 (6.8) g/day. Caloric composition of home diets showed that protein contributed 10-16%, fat 1 6 4 % and carbohydrates 45-71 YOof daily energy intakes. With the exception of vitamin A and C, the mean intakes of nutrients in the registration period were generally low (Table 3). Intakes of nutrients below 70% of the RDAs were most frequent for vitamin D (all), thiamin (five) and iron (six). Low intake of the different nutrients did not follow energy intake specifically.
ACTA PEDIATR 81 (1992)
Discussion When this study was undertaken (1987) 20 girls with Rett syndrome were identified in Norway. Prevalence figures for Rett syndrome in Sweden indicate a frequency of one case per 12-13000 girls (27). Girls with Rett syndrome constitute a small, but severely disabled group of handicapped children, whose demand for care and support increases with age. Growth retardation, feeding and nutritional problems are only some of the features that girls with Rett syndrome exhibit. In this study of 10 girls with Rett syndrome we found that growth retardation, underweight, reduced muscle mass and depleted energy stores were frequent. Two children failed to gain height and/or weight at the expected rate from 3-6 months of age, one from one year of age and four after two years of age. According to the parents, developmental delay was first suspected at a median age of one year (range from six months to two years of age). In 1986 physical growth was reported in 21 girls with Rett syndrome (12). In this study abnormal growth development was found in 18 (86%) of the patients, with 10 girls having linear growth below the 5th percentile of healthy children and eight girls exhibiting a fall off in growth during the first 1-4 years of life. From her study, Holm proposed that growth retardation and early fall off in expected growth could be useful markers in Rett syndrome (12). The results from our study revealed that the growth retardation had started after the parents had begun to suspect that “something was wrong” with the child, and in five of the cases, after the onset of the first feeding problems. Thus, relative to growth retardation, feeding problems and failure to follow normal feeding development may be an even earlier marker. Neither growth retardation nor feeding problems are, however, specific for Rett syndrome alone (19). In addition, our, as well as other case reports have shown that there are exceptions, namely girls who grow at the expected rate and even appear stubby (4). The diagnosis of Rett syndrome is usually tentative until stage I1 develops by 1-3 years of age (7, 27). The cause of growth retardation, as well as the etiology of Rett syndrome itself, are still unknown. Growth retardation is generally described as an inherent part of the progressive deterioration of higher brain functions and the resulting neurological abnormalities. Studies have not yet revealed significant explanations from metabolic disorders (28), intestinal dysfunctions or malabsorption symptomatology (29). As a consequence of the stereotypic hand movements and incessant hand-to-mouth movements, most girls with Rett syndrome develop oral-motor dysfunctions and poor self-feeding abilities (5, 9, 10, 13-15). In a previous report on the energy intake in disabled children, we found that children who have oral-motor dysfunctions and impaired self-feeding skills eat less compared to (allowances for age) their disabled counter-
Growth and nutrition in Rett syndrome
689
parts without feeding problems (25). In spite of good appetite, it may thus be proposed that reduced food intake is a contributing factor to growth retardation and wasting in girls with Rett syndrome due to longstanding mechanical feeding problems. All the patients for whom dietary records were obtained had energy intakes considerably below‘the mean allowance for age of healthy children. The evaluation of energy requirement for disabled children is difficult. Children with spasms and frequent involuntary movements may have relatively increased energy consumption, while the energy consumption in non-ambulatory children may be relatively decreased compared to healthy children (30). Increased energy rkquirement is also present in children who are going to catch-up previous growth retardation and wasting. The energy intake is calculated per kg body weight. In studies by Haas and colleagues (1 1 ,31,32), as well as in the present study, the girls had energy intakes per kg body weight above the allowances for healthy children. Haas and colleagues pinpointed the paradox that the patients were malnourished in spite of an above normal caloric intake. In their studies they have shown that girls with Rett syndrome may gain substantial weight on high energy, ketogenic diets, but it is still open to question whether the positive results can be ascribed to high fat content per se or to an increased total caloric intake. Taking into account that the girls have abnormally low weight, it is our opinion that the high energy intakes per kg body weight are “falsely” elevated compared to the allowances per kg body weight of healthy children. Thus, to compensate for growth retardation and lack of weight maintenance, we believe that the patients should be provided with substantially more calories than recommended for healthy children. In our study one girl was put on a diet without gluten after she was diagnosed autistic. According to the parents, the diet neither improved the growth nor the development of the child after one year. Another girl (patient no. 6) received a diet free from both gluten and lactose a t the time of study, but after a year and a half no clinical improvement was observed. Feeding problems in girls with Rett syndrome are of primary concern to parents and therapists (14). Several studies have demonstrated positive results with regard to improvement of mobility and posture and reduction of hand wringing and hand-to-mouth movements (1 0, 33-35). In a single case study, Sharpe & Ottenbacher (35) found a modest improvement in the amount of cereal consumed and in the time required to eat by use of elbow restraint. The therapy programs have made feeding easier for the parents (33). Stewart et al. (14) have suggested stage 111 of Rett syndrome as the best period for facilitating new motor skills, while every effort should be made to minimize the loss of functional skills during stages I1 and IV of the syndrome. We conclude that feeding problems and inadequate intake of energy and nutrients are likely to be contribut-
690
M Thommessen el al.
ing causes of lack of weight maintenance and poor growth in girls with Rett syndrome. Different nutritional intervention and therapy strategies such as increased number of meals per day, night meals (1 3), feeding of high-energy, high-fat diets (1 1, 3 1-32), vitamin and energy supplementation, tube feeding and gastrostomy (1 0) should be considered individually. Acknow/edgements.-This study was supported by the Norwegian Research Council for Science and the Humanities, and the Norwegian Research Council for Applied Social Science. The work was finished during employment at the Oslo Department of Environmental Health. The authors also gratefully acknowledge nutritionists Hege Araldsen, Jorunn Gran-Henriksen and h e Borgejordet for their help during data collection and the staff at Frambu Health Center, and the children and the parents for cooperation during the study.
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ACTA PEDIATR 81 (1992)
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