The role of GH insufficiency in the pathogenesis of short stature in Noonan syndrome is unclear. Cross-sectional study. Seventeen patients with Noonan syndrome (13 boys, 4 girls; aged 4.8-13.3 (mean 9.2) years) and short stature before start of GH treatment. Spontaneous 12-h overnight GH secretion by continuous sampling analysed using Pulsar, plasma IGF-I and IGFBP-3 levels, and 24-h urinary GH excretion were measured at start of GH treatment. A glucagon stimulation test was performed. Height and height velocity were monitored before and after 1 year of GH treatment. IGF-I and IGFBP-3 were remeasured after 1 year of GH treatment. Nine of the 17 children had a mean overnight GH concentration below the lower limit of the normal range. In six of the 17 patients, overnight GH profiles showed high trough GH concentrations. Glucagon stimulation tests were normal in 16 of the 17 patients. Mean IGF-I level was below normal (-0.4 SD). None of the parameters regarding GH secretion obtained from the overnight profile or provocative test was related to height or height velocity, nor to first year response to GH treatment. IGF-I and IGFBP-3 did not correlate with any of the GH secretion data. IGF-I and IGFBP-3 were related to height and height velocity at the start of GH treatment (r = 0.53 (P < 0.01) and r = 0.61 (P < 0.03) respectively). Rises in IGF-I and IGFBP-3 under GH treatment were related to the increment in height velocity (r = 0.70 (P < 0.01) and r = 0.71 (P < 0.02) respectively). Abnormalities in GH secretion are frequent in patients with Noonan syndrome and short stature. These abnormalities were not related to auxology at start of or response to GH treatment. Clinically GH insufficiency is not important in Noonan syndrome and monitoring spontaneous GH secretion is not necessary before the start of GH treatment.

An X-linked recessive disease with, in almost all patients, a fatal course in early childhood, occurring in a five-generation family is described. The 12 affected boys had early-onset floppiness, ataxia, liability to infections especially of the upper respiratory tract, deafness, and later, a flaccid tetraplegia and areflexia. Eleven boys died before the age of 5 years. One boy is still alive at the age of 12 years, but in addition to the above-mentioned signs, he must be ventilated at night and is nearly blind due to optic atrophy. In the only patient whose central nervous system could be examined at the time of autopsy, an almost complete absence of myelin in the posterior columns of the spinal cord was found. This may be the main pathological substrate for the neurological findings. No biochemical or immunological defects were detected. The family also counted 16 healthy male siblings and 13 definite of 28 possible female carriers. Some carriers developed a hearing impairment in early adulthood. As far as is known now, this disease has not been described before.

Objective -To assess whether physical growth is affected in early treated Dutch patients with phenylketonuria (PKU). Methods -The birth weights of all 137 early detected patients with PKU born in the period from 1974 to 1988 in the Netherlands were compared with reference values. Height, head circumference, and weight were measured at the age at which treatment started (commonly about 2-3 weeks), at 6 months of age, and yearly from the child's first birthday up to the age of 10 years. These measurements were compared with reference values. Results -The adjusted birth weight in patients with PKU was 141 g (95% confidence interval (CI) 66 to 216 g) less than Dutch reference values by Kloosterman and 103 g (95% CI 9 to 196 g) less compared with the birth weight ofanother reference group. At the age at which treatment started, z scores of patients for height by age were -0-23 (95% CI -0 44 to -0.02) and z scores for head circumference by age were -0 25 (95% CI -0 44 to -0.06). From the age at which treatment started up to the age of 3 years z scores for height by age further decreased to -0 74 (95% confidence interval -0 93 to -0.56), after which no additional decrease occurred. In contrast, z scores for head circumference increased from -0 25 at the first visit to 0-08 (95% CI -0-14 to 0.30) at the age of 1 year, after which they remained close to zero. Weight by height was close to the expected centiles for all ages. Conclusion -Patients with PKU are growth retarded at birth and have smaller head circumferences than the normal population. In Dutch patients further growth retardation occurs in the first three years of life.

Smith–Lemli–Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7‐dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7‐dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8–1 G > C splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS‐phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8–1 G > T). Two patients, homozygous for the IVS8–1 G > C mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS‐phenotype disclosed compound heterozygosity of the IVS8–1 G > C mutation in combination with different novel and known missense mutations.

Objective: To study the effect of suf®cient energy intake, by means of the protocolized administration of nasogastric tube feeding, on the nutritional status of a child with cancer. Design: A comparative experimental study. Setting: Tertiary care at the Centre for Pediatric Oncology, South East Netherlands, University Hospital, Nijmegen. Subjects: Seven children, newly diagnosed with cancer, were included in the experimental study and all completed the trial period. Fourteen patients were included in the retrospective study. They were randomly chosen from a group of patients previously treated for a malignancy at our department and who had received naso-gastric tube feeding for at least 16 weeks. Intervention: Protocolized (experimental group) vs non-protocolized (retrospective group) administration of naso-gastric tube feeding over a period of 16 weeks. The main difference was the amount of tube feeding administered. In addition to energy from other foods, children in the experimental group received 106 AE 13% of their total daily energy requirements (TDER) by means of tube feeding, whereas children in the retrospective group had received 75 AE 24%. Main outcome measures: Weight as a percentage of weight for height according to the 50th percentile of a healthy reference population ideal weight. Results: Weight, expressed as a percentage of the ideal weight, increased signi®cantly in the experimental group (18.2 AE 8.4; P 0.01) and the retrospective study group (5.2 AE 7.3; P 0.001). However, the increase was statistically signi®cant in favour of the experimental group (P 0.003), in which all the children reached their ideal weight, compared to 21% in the retrospective group. Conclusion: Aggressive protocolized nutritional intervention during the intensive phase of anti-cancer treatment, in the form of naso-gastric tube feeding that provides the child's total daily energy requirements, results in considerable improvement in the nutritional status.