From the Guidelines
Hypophosphatasemia is associated with severe complications, including rickets, osteomalacia, and disproportionate short stature in children, as well as hyperparathyroidism, enthesopathies, osteoarthritis, and pseudofractures in adults.
Implications of Hypophosphatasemia
The implications of hypophosphatasemia, a condition characterized by low alkaline phosphatase (ALP) levels, are multifaceted and can vary depending on the underlying cause. In the context of X-linked hypophosphataemia (XLH), a genetic disorder caused by mutations in the PHEX gene, hypophosphatasemia is a hallmark feature, leading to:
- Renal phosphate wasting, resulting in hypophosphatemia 1
- Elevated FGF23 levels, which contribute to the pathogenesis of the disease 1
- Diminished synthesis of active vitamin D, leading to rickets, osteomalacia, and other skeletal abnormalities 1
- Disproportionate short stature, dental abnormalities, and hearing loss 1
Clinical Characteristics
The biochemical characteristics of XLH include:
- Hypophosphatemia due to renal phosphate wasting 1
- Elevated ALP levels 1
- Elevated intact FGF23 levels 1
- Low or inappropriately normal circulating levels of 1,25(OH)2 vitamin D 1
Treatment and Management
Treatment of XLH typically involves oral phosphate supplementation and active vitamin D therapy, aimed at promoting growth, reducing bone pain, and improving dental health 1. However, conventional treatment may be associated with adverse effects, such as hypercalciuria and nephrocalcinosis 1. Recent advances in treatment, including the use of burosumab, a monoclonal antibody that neutralizes FGF23, offer new hope for patients with XLH 1.
From the Research
Implications of Hypophosphatasemia
The implications of hypophosphatasemia, a condition characterized by low alkaline phosphatase (ALP) levels, can be significant. Some of the key implications include:
- Bone and joint pain: Hypophosphatasemia has been linked to bone and joint pain, as well as stress fractures and premature tooth loss 2, 3, 4.
- Dental abnormalities: Dental abnormalities, such as tooth loss, have been reported in individuals with hypophosphatasemia 2, 4.
- Fatigue: Fatigue has been reported in some individuals with hypophosphatasemia, and in some cases, has been misdiagnosed as chronic fatigue syndrome or fibromyalgia 4.
- Increased risk of atypical femoral fractures: Individuals with hypophosphatasemia may be at increased risk of atypical femoral fractures, particularly if they are treated with antiresorptive medications such as bisphosphonates or denosumab 4.
- Misdiagnosis: Hypophosphatasemia can be misdiagnosed or underdiagnosed due to its nonspecific symptoms and lack of awareness among physicians 3, 5, 6.
Biochemical Implications
The biochemical implications of hypophosphatasemia include:
- Low ALP levels: Hypophosphatasemia is characterized by low ALP levels, which can be detected through blood tests 2, 3, 4, 5, 6.
- Elevated pyridoxal 5'-phosphate (PLP) levels: Elevated PLP levels have been reported in individuals with hypophosphatasemia, and may be used as a biomarker for the condition 2, 3, 4.
- Elevated urinary phosphoethanolamine (PEA) levels: Elevated PEA levels have also been reported in individuals with hypophosphatasemia, and may be used as a biomarker for the condition 2, 4.
Genetic Implications
The genetic implications of hypophosphatasemia include:
- Mutations in the ALPL gene: Mutations in the ALPL gene, which encodes the tissue-nonspecific ALP enzyme, have been identified in individuals with hypophosphatasemia 2, 3, 4.
- Heterozygous mutations: Many individuals with hypophosphatasemia have heterozygous mutations in the ALPL gene, which can result in mild symptoms 2, 3, 4.
- Homozygous or compound heterozygous mutations: Individuals with homozygous or compound heterozygous mutations in the ALPL gene may experience more severe symptoms and lower ALP levels 4.