Investigating intellectual disability: a genetic perspective.

Intellectual disability (ID) is a common paediatric problem. Investigation focused on determining the aetiology of ID is warranted because a specific diagnosis may assist in prognostication, recurrence risk counselling, and identification of therapeutic and educational interventions. Three groups of screening investigations can be justified on the basis of expert opinion, common sense and the small body of published evidence-based medicine. First, investigations where current evidence justifies routine use in the investigation of ID; second, investigations which should be considered in all children with ID, although there is insufficient current evidence to support routine use; and finally, investigations which currently have an unclear role in children with ID and should be restricted to specific clinical situations unless further evidence suggesting otherwise emerges. There is a great need for systematic evaluation of the diagnostic yield of investigation templates based on this proposed stratification of investigations.

Urine amino and organic acids analysis in developmental delay or intellectual disability.

OBJECTIVES: To determine the proportion of urine amino and organic acids screening tests (UMS) undertaken for patients referred with developmental delay or intellectual disability (DD/ID), and within the group with DD/ID, to determine the diagnostic yield, the proportion of diagnoses with a therapy and the associated recurrence risks. METHODS: A retrospective review of request forms and results of UMS, in individuals older than 28 days, referred to the Women's and Children's Hospital, North Adelaide, between 1 January 1992 and 31 December 1998 was carried out. Urine was analysed by ion exchange chromatography (amino acids), gas chromatography/mass spectrometry (organic acids), colorimetric assay (orotic acid) and stable isotope-dilution mass spectrometry (trimethylamine). RESULTS: A total of 3316 samples were received, 1447 being from patients with DD/ID. A diagnosis was determined for 1.8% of all referrals. For patients with DD/ID, the diagnostic yield was 1.1%, with a similar yield for isolated DD/ID and DD/ID with other features (9/828 vs 7/619; chi2 = 0.006; P = 0.93). Specific therapies were available for 69% of diagnoses associated with DD/ID and 87.5% had known Mendelian or mitochondrial inheritance. CONCLUSION: Urine metabolic screening is an important part of the evaluation of children with DD/ID as it can enable families to make reproductive decisions and children to receive appropriate therapy early.

Passive exposure to tobacco smoke and bacterial meningitis in children.

OBJECTIVE: To determine whether an association exists between passive exposure to tobacco smoke and bacterial meningitis in childhood, in an Australian population. METHODOLOGY: A retrospective, case-controlled telephone survey of the parents of 71 children admitted to the Women's and Children's Hospital, North Adelaide, with bacterial meningitis between 1990 and 1999. RESULTS: The annual incidence of Haemophilus influenzae type b (Hib) meningitis decreased significantly during the study period (11.0 cases per year 1991-93 and 1.5 cases per year 1994-99, Fisher's exact test; P < 0.001) whilst pneumococcal cases significantly increased (2.3 cases per year 1991-93 and 4.9 cases per year 1994-99, Fisher's exact test; P < 0.001). Although comparable numbers of cases and controls came from smoking families (41% vs 45%), more cases came from bi-parental smoking households (17% vs 8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) 0.77-6.24) and cases were more likely to live in households where parents smoked inside (27% vs 13%; OR 2.51, 95% CI 1.05-6.03). In households where parents smoked, children who had had meningitis were significantly more likely to have parents who smoked inside the house, than children who had not had meningitis (66% vs 28%, Fisher's exact test; P = 0.005). CONCLUSION: This study suggests there may be an association between high levels of passive exposure to tobacco smoke and bacterial meningitis in Australian children. A study with larger numbers of affected children which quantifies passive exposure to tobacco smoke is needed to determine the strength of this association.

Treatment of late-onset nonketotic hyperglycinaemia: effectiveness of imipramine and benzoate.

We report a patient with late-onset nonketotic hyperglycinaemia managed with a sequential approach to drug therapy in placebo-controlled therapeutic trials. Partial response to low-protein diet and sodium benzoate and dramatic response to imipramine are demonstrated, with parental scores on the Developmental Behavioural Checklist falling from the 86th centile before treatment to normal with combined benzoate and imipramine therapy.

Multiple acyl-coenzyme A dehydrogenase deficiency: diagnosis by acyl-carnitine analysis of a 12-year-old newborn screening card.

We report a family who experienced an unexplained neonatal death. Twelve years after the death, we retrospectively diagnosed multiple acyl-coenzyme A dehydrogenase deficiency by demonstrating an abnormal acyl-carnitine profile in the child's archived newborn screening card, using tandem mass spectrometry.

An ethical issue for reproductive technologies.

The establishment of "new birth technologies" (such as ovulation induction, in vitro fertilization and gamete intrafallopian transfer) has raised many ethical issues. One such issue is "selective fetal reduction", a process advocated in the management of excessive multiple pregnancy. The ethics of "selective fetal reduction" involve consideration of not only the efficacy of the process and the destruction of fetuses per se, but more specifically consideration of the moral dilemma of destroying some fetuses for the probable benefit of the remainder. The latter I consider here. Following from this ethical analysis it is suggested that the law regarding abortion should permit selective reduction in high multiple pregnancies, that is pregnancies of 4 or above. I contend that the law should prohibit deliberate exposure (in an infertility programme) to significant risk of high multiple pregnancy, when there is full intention to reduce any subsequent pregnancy of high multiple size.