Lysosomal storage disorders: A review of the musculoskeletal features.

The lysosomal storage disorders are a collection of progressive, multisystem disorders that frequently present in childhood. Their timely diagnosis is paramount as they are becoming increasingly treatable. Musculoskeletal manifestations often occur early in the disease course, hence are useful as diagnostics clues. Non-inflammatory joint stiffness or pain, carpal tunnel syndrome, trigger fingers, unexplained pain crises and short stature should all prompt consideration of a lysosomal storage disorder. Recurrent ENT infections, hepatosplenomegaly, recurrent hernias and visual/hearing impairment - especially when clustered together - are important extra-skeletal features. As diagnostic and therapeutic options continue to evolve, children with lysosomal storage disorders and their families are facing more sophisticated options for screening and treatment. The aim of this article is to highlight the paediatric presentations of lysosomal storage disorders, with an emphasis on the musculoskeletal features.

An observational study of type 2 diabetes within a large Australian tertiary hospital pediatric diabetes service.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is emerging as a significant clinical problem within the pediatric population. OBJECTIVE: The objective of this study was to identify patients with T2DM in a large tertiary hospital diabetes service and examine aspects relating to clinical course and management. METHODS: An initial audit of our diabetes service (over 6 yr) was followed by a 2-yr period of prospective case ascertainment to identify patients with T2DM. Comprehensive data collection was then undertaken in these individuals. RESULTS: Within our service (n = 1574), 33 young people with T2DM were identified. Significant levels of co-morbidity were evident - dyslipidaemia (56%), microalbuminuria (45%), hypertension (30%) and abnormal retinal findings (25%). Hypertension was more likely in those with greater initial and follow-up body mass index (BMI) [mean (SD) BMI: 36.3 (5.0) vs. 28.0 (6.3) kg/m(2) , p = 0.001, and 36.8 (5.3) vs. 28.5 (7.8) kg/m(2) , p = 0.007, respectively] and BMI standard deviation score (SDS) [mean (SD) BMI SDS: 2.34 (0.30) vs. 1.72 (0.66), p = 0.001, and 2.26 (0.31) vs. 1.38 (0.87), p < 0.001, respectively], whereas abnormal retinal findings were seen in those with higher HbA1c values at last appointment [geometric mean (range) 10.9 (8.4-13.6) vs. 7.4 (5.6-12.5)%, p = 0.01) and those with greater increases in HbA1c over time (+4.1 (3.1) vs. +0.2 (1.9)%, p = 0.009). Of the 33,9 (27%) were lost to follow-up. CONCLUSIONS: At present, T2DM in youth remains a low burden on our services. Patients with this diagnosis, however, have significant problems that present a major challenge to the development of effective management strategies.

In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth.

BACKGROUND: Polychlorinated biphenyls (PCBs) are industrial chemicals that were used widely for approximately 50 years. Now banned, they are still ubiquitous because of their persistence in the environment, the food chain, and human fatty tissue. High in utero exposures cause developmental deficits accompanied by growth retardation. Studies examining intrauterine growth at lower exposures have been inconsistent, with most such investigations having relied on surrogate exposure indicators such as consumption of fish from contaminated bodies of water. METHODS: In the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20 degrees C. At 5 years of age, detailed anthropometric measurements were made on children born in the years 1964-1967. We measured PCBs in specimens from 399 mothers using gas chromatography/electron capture detection. We conducted multiple linear regression to examine the relationship between these organochlorine concentrations and both intrauterine and 5-year growth, with adjustment for medical, lifestyle, sociodemographic, and specimen characteristics. RESULTS: In male infants, higher total in utero PCB exposure was associated with reduced birth weight, head circumference, and weight-for-gestational age. An increase from the 10th to 90th percentile in total PCBs was related to 290 g lower birth weight, a 0.7-cm decrease in head circumference, and for weight for gestational age, a reduction in z-score of 0.6. In girls, smaller head circumference and shorter gestations were observed. In contrast, prenatal PCBs were associated with greater growth in 5-year-old girls, with no apparent effect in 5-year-old boys. CONCLUSIONS: Maternally mediated exposure to PCBs may be detrimental to fetal growth, particularly in boys. These effects apparently are not persistent. Interpretation of greater childhood growth of girls is unclear.

Determinants of serum polychlorinated biphenyls and organochlorine pesticides measured in women from the child health and development study cohort, 1963-1967.

We examined predictors of organochlorine concentrations in serum specimens from women who were pregnant in the 1960s and participated in the Child Health and Development Study in the San Francisco Bay Area of California. That study enrolled pregnant women at the Kaiser-Permanente Medical Facilities, conducted interviews, and drew blood specimens; these specimens were centrifuged and the resulting serum specimens were frozen and placed in long-term storage. For the current investigation, organochlorines were measured by dual-column GC-electron capture detection in specimens collected in 1963-1967 from 399 pregnant women during the second and third trimesters. Using multiple linear regression models adjusted for serum lipids, we evaluated factors predicting concentrations of 11 polychlorinated biphenyl (PCB) congeners, their sum, and several pesticides and metabolites. Variables evaluated were age, race, place of birth, date of blood draw, body mass index, occupation, past residence on a farm, parity, and duration of pregnancy at blood draw. Concentrations of highly chlorinated PCBs and the sum of the PCBs increased with age. Concentrations of certain PCB congeners, as well as the sum, were significantly higher among nonwhites and increased with calendar date of blood draw. (italic)p,p(/italic) -DDT and (italic)p,p(/italic) -DDE concentrations were about 50% higher for nonwhites compared with whites and for those born in California or the southeastern United States versus elsewhere in the United States. Higher body mass index was associated with lower concentrations of several PCBs and (italic)p,p(/italic) -DDE but with higher heptachlor epoxide and DDT levels. The increase in use of PCBs during the 1960s is apparently detectable as increasing concentrations in maternal sera between 1963 and 1967. Marked racial and regional differences in serum pesticide levels were likely caused by geographic variation in previous agricultural and vector-control uses. The relationship to body mass index appears to be complex.