158 NUTRITION REVIEWS [Vol . 29. K O . 7

for the special dietary needs of patients with hereditary aminoacidopathies.

3. A broader repertoire of effective yet simple methods to deliver and monitor the existing modes of treatment must be developed. Patients could then be assured of all potential benefits in early diagnosis and treatment.

The issue can be summarized in terms of a meaningful commitment to individuals. Our society ,has apparently accepted the biological challenges to be found in genetic disease control. I t has found that there are cost benefits in early diagnosis and treatment of some forms of genetic disease, even though the number of our species affected by these illnesses is relatively small. Our civil codes tell us that the dignity and quality of these lives must be equal to that of others. Our technology should meet this challenge! If we will not accept it, we should dismantle our present genetic disease control apparatus and apply the resources and savings somewhere else.

Every reader of this commentary carries mutations which- couId place him and his offspring at risk in certain environments. Therefore, we . are. all members of the same constituency, and we must all participate in these decisions. The argument that we are tampering with our heredity by treating our mutants is probably of relatively

CELLULAR GROWTH IN

minor significance in many situations. If a “bad” gene can be neutralized by environmental .engineering tn make it harmless, then thac mutation is “bad” only when it exacts its full biologic cost, or if it demands an exorbitant price from society to neutralize it. Homo sapiens has proven before that he can reduce the latter price when he chooses to do so and we know that the former cost can often be virtually ablated. When such options are now available, we need not await the advent of genetic engineering to alter-our heredity in a presumably beneficial fashion. We did not wait to turn on our fur-bearing genes; we invented clothing and central heating. W e need not wait to change the alleles causing phenylketonuria and similar diseases, when we can provide effective therapy now. Under such circumstances the “morality” of a gene is only metaphysical. Our species can help its own mutants and when it does, the dignity of man finds very tangible expression.

Charles R. Scriver, M.D.* McGill University-Montreal Children’s

Hospital Research Institute deBelle Labomtory for Biochemical

Genetics, 2300 Tupper Street, Montreal 108. Quebec Canada

THE FAT ADOLESCENT.

Obesity in adolescence is accornpanicd by an inrmaw in lean tisrue os wcll as odipose tisaue. Diflerencez in the pattcrns of cellular ouergrowfh befween the #exes a n d among girls suggerf various causes for obesity and warn againct ouer-rimplificotion in the clinicol definition of the obese child.

Childhood obesity is a problem of increasing importance in affluent societies. Among the causes of obesity there may be some which are peculiar to infancy and childhood. Whatever the cause, the consequences of obesity in a child who is still growing are likely to

chffer from the effects of obesity in the adult. The complicated metabolic and hormonal imbalance associated with overeating may be expected to affect not

A limited number of reprints of this article m y be obtained from the author. THERE A R E NO REPRINTS OF REVIEWS.

July I 9 71 ] NUTRITION REVIEWS 159

only adipose tissue but also the composition of the lean body mass.

D. B. Cheek, R. B. Schultz, A. Parra, and R. C. Reba [Pediat. Res. 4, 268 (1970)] have attempted to analyze one facet of this complicated problem by measuring the composition o f muscle and adipose tissue in obese adolescents. Fourteen girls and nine boys were studied. The two groups may have been heterogeneous in the pathogenesis of their obesity, as one girl was found to have diabetes mellitus at the time of study and four had a family history of diabetes. All but four of the subjects had a family history of obesity. The age range of the boys studied was nine to 1 7 years and of the girls, six to 1 7 years. Each subject had been obese for two

.years or longer and weighed more than the ninety-seventh percentile for age.

In each subject, height and weight were measured and bone age was calculated from radiographs of the hand. Three 24-hour urine collections were made to determine the c rea t i ine excretion. A sample of fa t and gluteal muscle was taken from the buttock for analysis of protein and DNA in muscle, and of water, fat, protein, and collagen in the adipose tissue. The extracellular volume was measured using bromide. Total body potassium was estimated from measurements of 40K in a whole body counter. Total body water was determined using deuterium oxide. From these direct observations and measure- ments numerous other values were derived.

Lean body mass was calculated as a fraction of the total body water and the intracellular volume as the difference between the total body water and extracel!ular volume. Body fat was taken as the difference between body weight and the lean body mass. Earlier work had resulted in equations which prc- dicted the body fat for a normal person of a given height and by subtracting this

figure from that derived for total body fat a figure termed "excessive fatness" was obtained. By combining the meas- urements of muscle mass and those of muscle cell number from the biopsy, estimates were made of the total number of muscle cells in the body. By the same assumption that the biopsy sample was representative of the body as a whole, the total number of adipocytes in each subject was calculated.

There was a tendency for both the boys and girls to be taller than average and three of the giris were more than the ninety-seventh percentile for age. Of the 11 girls in whom bone age was measured there was an increase of more than 2 S.D. in two, but t he authors take five of this group as having an increased bone age and refer to them as a subgroup. Bone age was measured in four of the nine boys and was advanced more than 2 S.D. in one. Consequently no definite conclusion can be drawn regarding skeletal maturation in the obese boy. Total body water was significantly

greater than n o d in each of the seven obese boys and in nine of the 13 obese girls in whom measurements were made. Since lean body mass is calculated as total body water10.72, 18 of the 22 subjects 'had increased lean body mass. K was found to be unsatisfactory for

measuring lean body mas in obese subjects. The extracellular volume was reduced both in these obese boys and in the girls and consequently the intracellular volume, and hence the intracellular mass. was increased in most of the obese subjects.

Muscle biopsies were performed in five boys and 11 girls. The size of muscle cells in the obese children was normal. wilh the exception of the five girls with advanced bone age in whom the muscle cell size was lower than average. The musclc~ mass of the obese boys was within normal limits, but eight of thr o l w w prk. including the f ive with

160 NUTRITION REVIEWS [ VoL 29. No. 7

increased bone age, had a muscle mass more than 2 S.D. above the mean for normal children. By combining the results on muscle mass and cell size it follows that the obese boys had a total muscle cell number commensurate with their height, whereas the- girls with advanced bone age had a marked increase in the number of muscle cells.

The results for the analysis of the adipose tissue biopsies were compared with similar biopsies from four normal subjects aged 16 years. There were no differences between the obese boyz-and @. The obese children had a significantly lower percentage of protein and collagen and thus noncollagen protein as well. Since this WBS associated with an increase in the mean percentage of fat in the biopsy, the amount of fat per adipocyte was greater in both the obese boys and girls than in the control subjects.

From the analysis of the percentage of ht in the biopsy sample and the value derived for total body fat an estimate of total adipose tissue mass was made. The obese boys had more adipocytes and supporting tissue than the obese girls or control males. The obese girls were fat by virtue of having more lipid per adipocyte and had a similar number of adipocytes to female control subjects.

I t is not surprising that such detailed investigations of a small group of fat boys and girls should produce results which suggest heterogeneity within a group which was defined by clinical criteria. If the observations are of general applicability they may be summarised as follows: obese adolescents tend to be ta l l

for their age and have an increased lean body m a s in comparison with normal subjects of the same height. In obese boys the increased lean body mass does not reflect increased muscle mass which is normal for their length, but probably indicates in part an increase in the total a d i p o c j population. Obesity in adolescent boys is thus due to more fat per adipocyte and more adipocytes in the body. Obese girls are best subdivided into two subgroups for descriptive purposes. Both groups probably have a slight increase in the adipose tissue mas and much more fat per adipocyte than normal. Those with a normal bone age have a normal muscle mass and muscle cell population, whereas those with an advanced bone age have an increase in muscle mass, which Lq comprised of cells which are smaller than normal.

The description of three groups of obese adolescents in these terms may be of assistance to further work in elucidating the mechanisms of obesity in childhood. The suggestion of two types of obese girls serves as a waming against taking a simple clinical definition of obesity as the starting point for studies in' this field. I t may also suggest that different etiologies may be responsible for obesity within the subjects studied. Five of the girls had high birth weights but only one with advanced skeletal maturation fell into this group. These findings should lead to speculation and further study of the relative -contribu- tions of heredity, endocrine dysfunction, and nutritional insult in the pathogenesis of obesity in early life.

CHEMICAL DIAGNOSIS OF FETAL MALNUTRITION

Ccrloin Irukocylp mzymrr moy be r r d u r r d in ocl iv i ly in both malrrnol and /rkd blood during /t-/ol mo/nulri / iou.

lntra-uterine growth retardation has cent of 3,714 consecutive births (K. been estimated to account for 10 per E. Scott, and K. Usher, Am. J. Obstet.