Mineral Intake and Clinical Symptoms in Adult Patients with Hypophosphatasia

Background: Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of the tissue-nonspecific alkaline phosphatase entailing impaired turnover of phosphorus metabolites. Dietary mineral intake is suspected to influence clinical symptoms of HPP, but scientific evidence is missing.

Methods: Cross-sectional matched-pairs study collecting comprehensive data on nutrient intake in 20 HPP patients and 20 unaffected, age- and gender-matched controls. Dietary information and clinical symptoms were documented in detail over 7 consecutive days using structured diaries.

Results: Baseline data and type of energy-supplying nutrients were balanced between both groups. Median nutritional intake of phosphorus and calcium were significantly lower in HPP patients versus controls, which is partially attributable to lower energy consumption in HPP patients. Differences regarding phosphorus and calcium (Ca/P) ratio and uptake of magnesium, zinc, and vitamin B6 were not statistically significant. Both high (≥ 1375 mg/d) and low intakes (< 1100 mg/d) of phosphorus were significantly associated with an increased frequency of neuropsychiatric symptoms (P = 0.02). Similarly, very high and very low intake of calcium was significantly associated with musculoskeletal (P < 0.01), gastrointestinal (P = 0.02), and neuropsychiatric (P < 0.001) symptoms. An increased Ca/P ratio was associated with increased tiredness/fatigue (P < 0.01), whereas a decreased Ca/P was associated with gastrointestinal issues (P = 0.01).

Conclusion: Phosphorus and calcium intake seem reduced in HPP patients along with reduced total energy consumption. Particularly high as well as very low absolute or unbalanced phosphorus and calcium intake are associated with an increased frequency of clinical symptoms.

Keywords: calcium-phosphorus ratio; hypophosphatasia; nutritional intake; phosphorus intake.