Hypophosphatasia

Hypophosphatasia is also sometimes called:

• Rathbun disease
• HPP
• Phosphoethanolaminuria
• Other terms you may see: Odontohypophosphatasia and pseudohypophosphatasia

The usual abbreviation for hypophosphatasia is HPP.

Hypophosphatasia is caused by a genetic mutation. Genes are passed down from parent to child at random. It is important to remember we cannot control which genes we pass down to our children.

• There are many different forms of hypophosphatasia. Different forms vary in their age at which symptoms occur and their severity. The most severe forms of the disorder tend to occur before birth and in early infancy. The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. The different forms of hypophosphatasia include:
• Perinatal severe hypophosphatasia
• Perinatal benign hypophosphatasia
• Infantile hypophosphatasia
• Childhood, or juvenile, hypophosphatasia
• Adult hypophosphatasia
• Odontohypophosphatasia

Another term you may see: pseudohypophosphatasia

Perinatal hypophosphatasia is usually identified on ultrasound during pregnancy. Babies with perinatal severe hypophosphatasia have underdeveloped rib cages and short bowed arms and legs. Babies with this condition often have a severe complication called pulmonary insufficiency. Pulmonary, or respiratory, insufficiency is where the baby’s rib cage is too small for lungs to develop normally. Pulmonary insufficiency typically leads to death due to breathing difficulties. Some pregnancies affected with hypophosphatasia end in stillbirth.

Babies with prenatal benign hypophosphatasia are usually identified by ultrasound in pregnancy and are born with bowed arms/legs. These bone abnormalities often improve some as they age and look more like infantile hypophosphatasia. After their beginning symptoms improve, babies with prenatal benign hypophosphatasia have difficulty gaining weight and have early fusion of the skull bones (craniosynostosis). They can have bone softening and weakening. They may be more at risk for pneumonia because of weak rib bones and deformities in the chest. Babies can have low muscle tone (hypotonia) and high blood calcium levels (hypercalcemia).

Sometime children with infantile hypophosphatasia do not have any signs or symptoms at birth. They begin to show signs and symptoms within the first six months of life. Usually the first symptom is poor weight gain and poor growth. This is called failure to thrive. As they grow, their skull bones may fuse too early (craniosynostosis) and their head will start to look too wide (brachycephaly). Because of early skull fusion, babies with infantile hypophosphatasia can have increased pressure in the fluid around the brain (cerebrospinal fluid). This is called intracranial hypertension. Because of intracranial hypertension, babies with infantile hypophosphatasia can have headaches, optic disk swelling, and bulging eyes. The bones of babies with infantile hypophosphatasia are soft and weak. They can develop rickets, which is a softening and weakening of the bones. Some babies with infantile hypophosphatasia have chest and rib deformities. This causes them to have difficulty breathing and can make them at a higher risk of pneumonia. Some babies with infantile hypophosphatasia have low muscle tone (hypotonia) and swelling in their wrists and ankles. Because calcium is not deposited into the bones correctly, babies with infantile hypophosphatasia can have high calcium levels in their blood (hypercalcemia). Hypercalcemia can cause vomiting, constipation, weakness, and poor feeding.

Children with childhood hypophosphatasia can have very different degrees of signs and symptoms. Some children have rickets, a softening and weakening of the bones, that begins between the ages of 2-3 and have a higher risk of bone breaks. Some children with childhood hypophosphatasia have early fusion of their skull bones (craniosynostosis).

People with adult hypophosphatasia can have softening of their bones later in life (osteomalacia). Some adults with adult hypophosphatasia report having rickets (softening and weakening of the bones) as a child or losing their baby teeth earlier than usual. People with adult hypophosphatasia have a higher risk of breaking their bone or having stress fractures. Bone pain and joint pain is often reported.

Ondontohypophosphatasia is characterized by early tooth loss in childhood or loss of adult teeth. There are generally no other signs or symptoms.

Because of poor mineralization, people with hypophosphatasia can have high blood calcium levels. When this happens, calcium crystals can build up in the cartilage of joints (called chondrocalcinosis). This can damage the joints and cause pain.

Rickets is a condition that happens when there is poor mineralization in bones that are growing that causes bones to soften and weaken. In hypophosphatasia, rickets is caused when mineralization does not happen because of a mutation in the ALPL gene.