Assessment of Motor Milestones in Twins

The aim of this study was to investigate the reliability of obtaining through mailed surveys maternal reports of specific major motor milestones achievement. To accomplish this aim we compared and contrasted mailed survey data and telephone interview data on a series of questions about age at which motor milestones were achieved. We used monthly telephone interviews with mothers of 238 twin pairs, beginning at age 6 months, which ascertained the age at which each specific milestone was met. The contrasting 'through the mail' survey was sent after the second birthday of an independent group of children, and included 463 twin pairs. All twins were born between March 2003 and March 2004. Comparisons were made for the following 5 milestones: sitting without support, hands and knees crawling, turning from back to belly, standing without support, and walking without support. There was no difference between the concurrent telephone interviews and the retrospective through the mail survey on any of the landmarks, except 'standing without support'. From this work we conclude that data on achieving milestones can be reliably obtained through the mail using retrospective surveys when the children are 2 years of age

High childhood serum triglyceride concentrations associate with hepatocellular adenoma development in patients with glycogen storage disease type Ia

Background & Aims: Glycogen storage disease type Ia (GSDIa) is an inborn error of carbohydrate metabolism caused by pathogenic variants in the glucose-6-phosphatase catalytic subunit 1 (G6PC1) gene and is associated with hepatocellular adenoma (HCA) formation. Data on risk factors for HCA occurrence in GSDIa are scarce. We investigated HCA development in relation to sex, G6PC1 genotype, and serum triglyceride concentration (TG). Methods: An observational study of patients with genetically confirmed GSDIa ≥12 years was performed. Patients were categorised for sex; presence of 2, 1, or 0 predicted severe G6PC1 variant (PSV); and median TG during childhood (5.65 mmol/L was associated with HCA development at younger age, compared with patients with childhood TG 5.65 mmol/L as an independent risk factor for HCA development (hazard ratio [HR] 6.0; 95% CI 1.2–29.8; p = 0.028). Conclusions: In patients with GSDIa, high childhood TG was associated with an increased risk of HCA, and earlier onset of HCA development, independent of sex-associated hypertriglyceridaemia, and G6PC1 genotype. Lay summary: Glycogen storage disease type Ia (GSDIa) is a rare, inherited metabolic disease that can be complicated by liver tumours (hepatocellular adenomas), which in turn may cause bleeding or progress to liver cancer. Risk factors associated with hepatocellular adenoma formation in patients with GSDIa are largely unknown. In our study, we found that high serum triglyceride concentrations during childhood, but not specific genetic variants, were associated with increased risk of hepatocellular adenoma diagnosis later in life

High protein prescription in methylmalonic and propionic acidemia patients and its negative association with long-term outcome

Background and objective: Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inborn errors of metabolism. While survival of MMA and PA patients has improved in recent decades, long-term outcome is still unsatisfactory. A protein restricted diet is the mainstay for treatment. Additional amino acid mixtures (AAM) can be prescribed if natural protein is insufficient. It is unknown if dietary treatment can have an impact on outcome. Design: We performed a nationwide retrospective cohort study and evaluated both longitudinal dietary treatment and clinical course of Dutch MMA and PA patients. Protein prescription was compared to the recommended daily allowances (RDA); the safe level of protein intake as provided by the World Health Organization. The association of longitudinal dietary treatment with long-term outcome was evaluated. Results: The cohort included 76 patients with a median retrospective follow-up period of 15 years (min–max: 0–48 years) and a total of 1063 patient years on a protein restricted diet. Natural protein prescription exceeded the RDA in 37% (470/1287) of all prescriptions and due to AAM prescription, the total protein prescription exceeded RDA in 84% (1070/1277). Higher protein prescriptions were associated with adverse outcomes in severely affected patients. In PA early onset patients a higher natural protein prescription was associated with more frequent AMD. In MMA vitamin B12 unresponsive patients, both a higher total protein prescription and AAM protein prescription were associated with more mitochondrial complications. A higher AAM protein prescription was associated with an increased frequency of cognitive impairment in the entire. Conclusion: Protein intake in excess of recommendations is frequent and is associated with poor outcome