Bone Mineral Density in Patients with Hepatic Glycogen Storage Diseases.

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9-20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ -2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ -2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.

Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients.

INTRODUCTION: The association between the BTD genotype and biochemical phenotype [profound biotinidase deficiency (BD), partial BD or heterozygous activity] is not always consistent. This study aimed to investigate the genotype-biochemical phenotype association in patients with low biotinidase activity. METHODS: All exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian individuals who exhibited low biotinidase activity. For each patient, the expected biochemical phenotype based on the known genotype was compared with the observed biochemical phenotype. Additional non-genetic factors that could affect the biotinidase activity were also analysed. RESULTS: Most individuals were identified by neonatal screening (n = 66/72). When consecutive results for the same patient were compared, age, prematurity and neonatal jaundice appeared to affect the level of biotinidase activity. The biochemical phenotype at the time of the second blood collection changed in 11/22 patients compared to results from the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G (p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented different biochemical phenotypes. The expected and observed biochemical phenotypes agreed in 68.5% of cases (concordant patients). The non-coding variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17 discordant patients. In addition, c.-183G>A and c.-514C>T were also present in 10/37 concordant patients. CONCLUSIONS: The variants found in the promoter region do not appear to have a strong impact on biotinidase activity. Since there is a disparity between the BTD genotype and biochemical phenotype, and biotinidase activity may be affected by both genetic and non-genetic factors, we suggest that the diagnosis of BD should be based on more than one measurement of plasma biotinidase activity. DNA analysis can be of additional relevance to differentiate between partial BD and heterozygosity.