Agnieszka Konopka

Background: Hypophosphatasia (HPP) is a rare genetic disorder caused by a loss-of-function mutation in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Reduced TNSALP activity in HPP primarily leads to bone mineralization disorders. Given the complex and challenging nature of issues related to vitamin D and HPP, it is essential to evaluate each patient individually and adjust the appropriate dose of vitamin D according to their specific needs in order to maintain calcium phosphate homeostasis and normal vitamin D levels. Maintaining proper vitamin D homeostasis in patients with hypophosphatasia is one of the greatest challenges. Objective: The objective of this study was to conduct a retrospective, comprehensive assessment of calcium–phosphate metabolism, with particular emphasis on vitamin D status in patients with genetically confirmed hypophosphatasia (HPP), and to identify potential correlations between 25(OH)D concentrations and other parameters of calcium–phosphate in this group of patients. Methods: A single-center, retrospective pilot study was conducted in a small cohort (n = 36) of patients suffering from an ultra-rare genetic disorder, hypophosphatasia. The small sample size reflects the ultra-rare nature of the disease; so far, HPP has been diagnosed in approximately 50 patients in Poland (prevalence 1:300,000). The analysis included medical records of patients. Results: Vitamin D deficiency was not observed in the majority of patients with hypophosphatasia in the study group. The initiation of long-term enzyme replacement therapy (with asfotase alfa) did not significantly affect the annual change in mean serum vitamin D concentration. As established in the literature, growth disorders are an inherent feature of the clinical picture of hypophosphatasia. This was reflected in our study group, where nearly half of the pediatric patients achieved a height below the 10th percentile. Conclusions: Within this limited sample, these growth issues did not appear to be associated with disturbances in calcium and phosphate metabolism or vitamin D deficiency.

Background: Familial hypercholesterolemia (FH) is a genetic autosomal co-dominant metabolic disorder leading to elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Early development of atherosclerotic cardiovascular disease (ASCVD) is common in affected patients. We aimed to evaluate the characteristics and differences in the diagnosis and therapy of FH children and adults. Methods: All consecutive patients who were diagnosed with FH, both phenotypically and with genetic tests, were included in this analysis. All patients are a part of the European Atherosclerosis Society FH-Study Collaboration (FHSC) regional center for rare diseases at the Polish Mother’s Memorial Hospital Research Institute (PMMHRI) in Lodz, Poland. Results: Of 103 patients with FH, there were 16 children (15.5%) at mean age of 9 ± 3 years and 87 adults aged 41 ± 16; 59% were female. Children presented higher mean levels of total cholesterol, LDL-C, and high-density lipoprotein cholesterol (HDL-C) measured at the baseline visit (TC 313 vs. 259 mg/dL (8.0 vs. 6.6 mmol/L), p = 0.04; LDL 247 vs. 192 mg/dL (6.3 vs. 4.9 mmol/L), p = 0.02, HDL 53 vs. 48 mg/dL (1.3 vs. 1.2 mmol/L), p = 0.009). Overall, 70% of adult patients and 56% of children were prescribed statins (rosuvastatin or atorvastatin) on admission. Combination therapy (dual or triple) was administered for 24% of adult patients. Furthermore, 13.6% of adult patients and 19% of children reported side effects of statin therapy; most of them complained of muscle pain. Only 50% of adult patients on combination therapy achieved their treatment goals. None of children achieved the treatment goal. Conclusions: Despite a younger age of FH diagnosis, children presented with higher mean levels of LDL-C than adults. There are still urgent unmet needs concerning effective lipid-lowering therapy in FH patients, especially the need for greater use of combination therapy, which may allow LDL-C targets to be met in most of the patients.