Osteomalacia And Vitamin D, What Is The Link?

Dr. Michael Holick Speaks on Osteomalacia and its link to Vitamin D deficiency.

What is Hypophosphatasia (HPP)?

Hypophosphatasia is an inherited metabolic (chemical) bone disease that results from low levels of an enzyme called alkaline phosphatase (ALP). Enzymes are proteins that act in the body's chemical reactions by breaking down other chemicals. ALP is normally present in large amounts in bone and liver. In hypophosphatasia, abnormalities in the gene that makes ALP lead to production of inactive ALP. Subsequently, several chemicals - including phosphoethanolamine, pyridoxal 5'-phosphate (a form of vitamin B6) and inorganic pyrophosphate - accumulate in the body and are found in large amounts in the blood and urine of people with Hypophosphatasia. It appears that the accumulation of inorganic pyrophosphate is the cause of the characteristic defective calcification of bones in infants and children (rickets) and in adults (osteomalacia).

Nevertheless, the severity of hypophosphatasia is remarkably variable from patient-to-patient. The most severely affected fail to form a skeleton in the womb and are stillborn. The most mildly affected patients may show only low levels of ALP in the blood, yet never suffer bony problems.

In general, patients are categorized as having "perinatal", "childhood" or "adult" hypophosphatasia depending on the severity of the disease, which in turn is reflected by the age at which bony manifestations are first detected. Odontohypophosphatasia refers to children and adults who have only dental, but not skeletal, problems (premature loss of teeth).

The x-ray changes are quite distinct to the trained eye. Similarly, the diagnosis of hypophosphatasia is largely substantiated by measuring ALP in the blood (a routine test) that is low in hypophosphatasia. However, it is important that the doctors use appropriate age ranges for normals when interpreting an ALP level.

Prevalence

It has been estimated that severe forms of hypophosphatasia occur in approximately one per 100,000 live births. The more mild childhood and adult forms are probably somewhat more common. About one out of every 200 individuals in the United States may be a carrier for hypophosphatasia

Prognosis

The outcome following a diagnosis of hypophosphatasia is very variable. In general, the earlier the diagnosis is made the more severe the skeletal manifestations. Cases with severe, not mild, deformity at birth almost always have a lethal outcome within days or weeks. When the diagnosis is made before six months of age, some infants have a downhill and fatal course, others survive and may even do well. When diagnosed during childhood, there can by presence or absence of skeletal deformity from underlying rickets, but premature loss of teeth (less than five years of age) is the most common manifestation. Adults may be troubled by recurrent fractures in their feet and painful, partial fractures in their thigh bones.

Symptoms

Depending on the severity of the skeletal disease, there may be deformity of the limbs and chest. Pneumonia can result if chest distortion is severe. Recurrent fractures can occur. Teeth may be lost prematurely, have wide pulp (inside) chambers, and thereby be predisposed to cavities.

Inheritance Factors

The severe perinatal and infantile forms of hypophosphatasia are inherited as autosomal recessive conditions. The patient receives one defective gene from each parent. Some more mild (childhood or adult) hypophosphatasia cases are also inherited this way. Other mild adult and odonto hypophosphatasia cases seem to be inherited in an autosomal dominant pattern (the patient gets just one defective gene, not two, transmitted from one of his/her parents). In this form, mild hypophosphatasia can occur from generation-to-generation. The perinatal form of hypophosphatasia can often be detected during pregnancy by ultrasound and by measuring ALP activity in chorionic villus samples from amniocentesis.

Individuals with hypophosphatasia and parents of children with hypophosphatasia are encouraged to seek genetic counseling to explain the likelihood and severity of hypophosphatasia recurring in their families.

Treatments

As yet, there is no cure for hypophosphatasia and no proven medical therapy. Some medications are being evaluated. Treatment is generally directed towards preventing or correcting the symptoms or complications.

Expert dental care and physical therapy are recommended. An orthopaedic procedure called "rodding" may be especially helpful for adults with painful partial fractures in their thigh bones. Severely affected infants may manifest increased levels of calcium in their blood that may be treated with calcitonin and certain diuretics. Doctors should avoid the temptation to give calcium supplements or vitamin D unless there is clear-cut deficiency.

Contributing Medical Specialist
Michael P. Whyte. M.D.
Medical Director
Center for Metabolic Bone Disease and Molecular Research
Shriners Hospital
St. Louis, Missouri

So they want to move our son...

The McMinnville CPS decided that it would be okay to move our almost 5 month old son to another foster home today. Some how they seem to think they can follow their own rules and avoid the law and just ignore using a family placement. As many of you know, our son should never have been taken from us in the first place because he has a medical issue and was not in any way abused or neglected.. But McMinnville CPS doesn't seem to care. In fact, they are even going against what Honorable Judge Tichenor stated in our disposition hearing where he didn't want our son to have to suffer from bonding issues. Yet, despite all of that, CPS thinks that putting our son with family isn't very important.


This is a section from the email our caseworker sent us:


"Thirdly, [Your son] had been referred and was seen by Dr. Madison, an endocrinologist at OHSU today.  The doctor asked about his history, even though she has received all of the previous notes/labs and she gave him a thorough examination.  Blood was drawn for a panel which will test various bone/blood levels, including his vitamin D and phosphate.  The results will be sent to DHS and Dr. Whittaker, who referred him.  Dr. Whittaker is not referring him for a third bone scan of his ribs.  At the time of his testimony he had not seen the second scan.  Now that he has, he is not referring for another scan.

Finally, I contacted [Linda's cousin-in-law], who indicated that her and her husband [Linda's cousin] want to be the resource for [your son].  The assigned certifier has attempted to contact them two times over the past week and has received no phone calls back.  Also, [family friend] has not contacted the certifier either.  Please understand that I am working to get him into a relative placement.  He will be moved to another foster home on Monday 2/27/12, in McMinnville, and will remain there until DHS can certify a relative and can place [your son] there."

The reason they are moving our son according to the CASA worker is: "All I know is that the current foster mom has a family emergency which forced her to ask DHS to remove [the baby] asap.  Also, per an email to your client on Wednesday from DHS, family members who have offered to be placements for Joss have not followed thru.  Linda should have been able to tell you that." Clearly she hasn't been paying attention to what has been going on, and clearly she isn't looking out for the best interest of our son.

From conversations with numerous family members it has been made very clear that there has not been an attempt to contact anyone. DHS/CPS isn't being honest, and we have our entire family group to testify to that. It is clearly wrong for CPS to pretend that they are trying to help our son or anyone in our family. The longer they have him in their custody, the more money they get. Our son has a medical condition, and they don't want to be proven wrong. We will continue to fight for what is right and true, and we will prevail. Just wait.