T1DM children and adolescents have impaired bone metabolism which seems to be multifactorial. Reduced osteoblast and increased osteoclast signaling, resulting from multiple simultaneous disturbances, could lead to reduced peak bone accrual in early adulthood, predisposing to adult osteopenia and osteoporosis.

Background:There is evidence in support of low bone density in young patients with disorders of phenylalanine metabolism; however, little is known about muscle and fat mass in these patients, especially in those with mild hyperphenylalaninemia (mHPA).Objectives:We aimed to evaluate body composition of children and adolescents with early-diagnosed disorders of phenylalanine metabolism.Patients and Methods:The study was conducted in the Institute of Child Health, which is the national center that performs newborn screening. Bone, muscle, and fat mass of 48 patients with phenylketonuria (PKU) and 32 patients with mild mHPA, aged five to 18 years, were compared to 57 age- and sex-matched controls. Dual energy X-ray absorptiometry was used for this purpose.Results:Compared to controls, bone mineral density (BMD) was lower in patients with PKU (mean total body BMD z score, 0.11; P = 0.03) and in those with mild mHPA (mean lumbar BMD z score, -0.34; P = 0.01). Lean body mass and fat mass were not significantly affected in the study group. Comparison between the two patients groups did not reveal any difference in body composition profiles; however, pubertal status appeared important for within-group comparisons. Fat mass was significantly increased in teenagers with PKU, which was more evident in those with poor dietary compliance irrespective of gender (fat mass z score, 0.66; P = 0.018). Finally, positive correlations were found not only between bone, muscle, and fat mass in both groups, but also between fat mass and Phenylalanine levels in patients with PKU (r, 0.46; P = 0.001).Conclusions:Bone mineral density appears suboptimal in young patients with disorders of phenylalanine metabolism. Adolescents seemed more prone to obesity, especially when their dietary adherence was poor, whereas muscle mass was not considerably affected. To ensure healthier bones and less fat content, close follow-up as well as proper lifestyle advice is needed.

Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5΄-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births, while the estimated prevalence of the less severe adult form is estimated to be between 1:3100 to 1:508, in different countries in Europe. Presentation largely varies, ranging from death in utero to asymptomatic adults. In infants and children, clinical features include skeletal, respiratory and neurologic complications, while recurrent, poorly healing fractures, muscle weakness and arthropathy are common in adults. Persistently low serum alkaline phosphatase is the cardinal biochemical feature of the disease. Management requires a dedicated multidisciplinary team. In mild cases, treatment is usually symptomatic. Severe cases, with life-threating or debilitating complications, can be successfully treated with enzyme replacement therapy with asfotase alfa.

Introduction: Previous studies have reported an association between classic galactosemia (CG) and decreased bone mass. The primary objective of this systematic review with meta-analysis was to determine the extent of bone mineral density (BMD) Z-score reduction. Low BMD was defined as a Z-score À2 standard deviations (SD). The secondary objective was to evaluate other indicators of bone status through a descriptive analysis.Methods: Systematic search strategies were developed by an experienced clinical librarian. Selection of relevant manuscripts, risk of bias assessment, and data extraction were performed independently by two investigators.Results: Four studies were included in the meta-analysis. BMD Z-scores in children and adults with CG measured at the lumbar spine (LBMD; 4 studies; n ¼ 112), total hip (HBMD; 2 studies; n ¼ 58), and femoral neck (FBMD; 2 studies; n ¼ 73) were assessed. Mean BMD Z-scores in the CG population were LBMD À0.70 (95% CI: À0.88, À0.52); HBMD À0.89 (95% CI: À1.14, À0.64); and FBMD À0.63 (95% CI À1.29, 0.02). Results from studies included in the descriptive analysis (n ¼ 7) show that vitamin D levels were frequently in the low reference range, whereas serum calcium levels were within reference range.Communicated by: Alberto B. Burlina, MDThe authors "Britt van Erven" and "Lindsey Welling" are equal first authors.The authors "M. Estela Rubio-Gozalbo" and "Annet M. Bosch" are equal first authors. Electronic supplementary material:The online version of this chapter