CD-ROM Today (UK) (Spanish) 15/CDRT.iso/dp/0385/03853.txt

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$Unique_ID{BRK03853}
$Pretitle{}
$Title{Hypophosphatasia}
$Subject{Hypophosphatasia HHRH Hypercalciuric Rickets Hypophosphatemic Rickets
with Hypercalciuria, Hereditary Hypophosphatasia, Infantile (Neonatal)
Hypophosphatasia, Childhood Hypophosphatasia, Adult Includes:
Pseudohypophosphatasia Rickets Hypophosphatemic Rickets (Vitamin D-Resistant
Rickets; X-Linked Hypophosphatemia) Osteomalacia Pseudovitamin D Deficiency
Rickets (Vitamin D-Dependent Rickets, Type I) Osteogenesis Imperfecta }
$Volume{}
$Log{}

Copyright (C) 1988, 1989, 1990 National Organization for Rare Disorders,
Inc.

518:
Hypophosphatasia

** IMPORTANT **
It is possible the main title of the article (Hypophosphatasia) is not
the name you expected.  Please check the SYNONYMS listing on the next page to
find alternate names and disorder subdivisions covered by this article.

Synonyms

     HHRH
     Hypercalciuric Rickets
     Hypophosphatemic Rickets with Hypercalciuria, Hereditary

DISORDER SUBDIVISIONS:

     Hypophosphatasia, Infantile (Neonatal)
     Hypophosphatasia, Childhood
     Hypophosphatasia, Adult

     Includes:  Pseudohypophosphatasia

Information on the following disorders can be found in the Related
Disorders section of this report:

     Rickets
     Hypophosphatemic Rickets (Vitamin D-Resistant Rickets; X-Linked
Hypophosphatemia)
     Osteomalacia
     Pseudovitamin D Deficiency Rickets (Vitamin D-Dependent Rickets, Type I)
     Osteogenesis Imperfecta
     Paget's Disease

General Discussion

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Hypophosphatasia is a genetic metabolic bone disorder characterized by
skeletal defects resembling those of Rickets.  The symptoms result from a
failure of bone mineral to be deposited in young, uncalcified bone (osteoid),
and in the cartilage at the end of the long bones (epiphyses) during early
years.  The activity of the enzyme alkaline phosphatase in blood serum and
bone cells is lower than normal.  Urinary excretion and blood plasma
concentrations of phosphoethanolamine and inorganic pyrophosphate are
abnormally high.  Unlike other forms of Rickets, Hypophosphatasia does not
respond to treatment with vitamin D.

Symptoms

DISORDER SUBDIVISIONS

Infantile Hypophosphatasia:
This is the most common form of the disorder, usually beginning before 6
months of age.  It can be diagnosed before birth.  In infants affected with
Hypophosphatasia, defective bone hardening (mineralization) is often
associated with increased pressure inside the skull which may result in
bulging eyes (exophthalmos).  There may be excessive levels of calcium in the
blood (hypercalcemia) and urine (hypercalciuria).  Calcium may accumulate in
the little tubes of the kidneys, sometimes resulting in kidney failure.  The
bones usually become weak and bent, resembling Rickets.  Bone abnormalities
can be severe.

Childhood Hypophosphatasia:
This form of the disorder usually begins after 6 months of age.  It is
characterized by premature loss of baby teeth, increased susceptibility to
infections, and slowed growth.  X-rays show irregularities in the tips
(epiphyses) and shafts of the long bones.  Spontaneous healing of Rickets-
like (rachitic) bone changes may occur in this form of Hypophosphatasia.

Adult Hypophosphatasia:
This form of Hypophosphatasia is quite rare.  It is characterized by a
history of Rickets symptoms and premature loss of baby teeth during
childhood.  The permanent teeth are often lost or extracted during early
adulthood.  The bones are less dense than normal and fractures tend to occur
more often than in the general population.

Pseudohypophosphatasia:
Patients with Pseudohypophosphatasia have all or many of the
manifestations of Hypophosphatasia.  However, blood concentrations of the
enzyme alkaline phosphatase are normal.

Causes

The symptoms of Hypophosphatasia are caused by a deficiency of the enzyme
alkaline phosphatase.  The Infantile and Childhood forms of the disorder are
inherited through autosomal recessive genes.  The Adult form is inherited
through autosomal dominant genes.

Human traits including the classic genetic diseases, are the product of
the interaction of two genes for that condition, one received from the father
and one from the mother.

In recessive disorders, the condition does not appear unless a person
inherits the same defective gene from each parent.  If one receives one
normal gene and one gene for the disease, the person will be a carrier for
the disease, but usually will show no symptoms.  The risk of transmitting the
disease to the children of a couple, both of whom are carriers for a
recessive disorder, is twenty-five percent.  Fifty percent of their children
will be carriers, but healthy as described above.  Twenty-five percent of
their children will receive both normal genes, one from each parent and will
be genetically normal.

In dominant disorders, a single copy of the disease gene (received from
either the mother or father) will be expressed "dominating" the normal gene
and resulting in appearance of the disease.  The risk of transmitting the
disorder from affected parent to offspring is 50% for each pregnancy
regardless of the sex of the resulting child.

Affected Population

Hypophosphatasia is a rare disorder.  The different forms of this disorder
all affect males and females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to Hypophosphatasia.
Comparisons may be useful for a differential diagnosis:

Rickets
Several forms of Rickets exist, all of which are characterized primarily
by weakening of bones due to abnormal calcium metabolism as well as possible
decreases of other substances in the body.  Rickets may be either acquired or
inherited.  In cases caused by dietary deficiency of Vitamin D, a supplement
to the diet can cure the disease when given before the bones are fully
developed.

Hypophosphatemic Rickets is a rare genetic form of Rickets characterized
by impaired transport of phosphate in the body, combined with diminished
Vitamin-D metabolism in the kidneys.  Additionally, calcium and phosphate are
not absorbed properly in the intestines which can lead to softening of bones.
Major symptoms include skeletal changes, weakness and slowed growth.  Cases
affecting females are usually less severe than those affecting males.  One
rare acquired form of this disorder may be associated with a benign tumor.
(For more information on this disorder, choose "Hypophosphatemic Rickets" as
your search term in the Rare Disease Database.)

Osteomalacia is a disorder characterized by gradual softening and bending
of the bones.  Pain may occur in various degrees of severity.  Softening
occurs because of deficient levels of calcium in bones due to diminished
amounts of vitamin D or a kidney dysfunction.  This illness is more common
among women than men, and often begins during pregnancy.  It can exist alone
or in association with other disorders, such as Hypophosphatemic Rickets.

Pseudovitamin D Deficiency Rickets (Vitamin D-Dependent Rickets, Type I)
is characterized by severe skeletal changes (such as bending of the bones)
and weakness.  Symptoms are caused by abnormal vitamin-D dependent
metabolism.  The disorder is inherited as an autosomal recessive trait.  This
type of Rickets often begins during early infancy.  Blood levels of calcium
are severely diminished in patients with Vitamin-D Dependent Rickets,
although phosphate levels appear normal or only slightly deficient.  Amino
acids are lost in the urine due to a kidney dysfunction.  Occasional muscle
cramps may occur.  Convulsions and abnormalities of the spine and pelvis may
also develop.

Osteogenesis Imperfecta, or Brittle Bone Disease, is a group of
hereditary connective tissue disorders characterized by unusual bone
fragility and a tendency of bones to fracture easily.  Traditionally, the
disorder has been recognized in two forms.  Osteogenesis Imperfecta Congenita
is apparent at birth, while Osteogenesis Imperfecta Tarda manifests itself
only later, usually at 3 or 4 years of age, and is a milder disorder.
Osteogenesis is a relatively common birth defect, with an incidence in the
United States of 1 in 20,000 to 50,000 births.  (For more information on this
disorder, choose "Osteogenesis Imperfecta" as your search term in the Rare
Disease Database.)

Paget's Disease is a slowly progressive disorder of the skeletal system
characterized by abnormally rapid bone formation and breakdown, leading to
the development of bones that are dense but fragile.  Some bones may also be
bent.  It usually affects middle-aged and elderly people and most frequently
occurs in the spine, skull, pelvis, thighs and lower legs.  (For more
information on this disorder, choose "Paget Disease" as your search term in
the Rare Disease Database.)

Therapies:  Standard

Hypophosphatasia can be diagnosed before birth because the unhardened
(uncalcified) skull does not show up clearly in ultrasound pictures.  This
disorder can be distinguished from Anencephaly by analysis of the substance
alpha-fetoprotein, which is normal in fetuses with Hypophosphatasia, and high
in those with Anencephaly.

Treatment with Vitamin D and its breakdown products (metabolites) has not
been successful in Hypophosphatasia and other forms of Vitamin-D resistant
Rickets.  Sustained oral phosphate supplements may be beneficial in some
cases.  Other treatment is symptomatic and supportive.


Genetic counseling is recommended for families of persons with
Hypophosphatasia.

For more information for parents and physicians dealing with
Hypophosphatasia patients, please contact Dr. Michael Whyte listed in the
Resource section.

Therapies:  Investigational

A few cases of Infantile Hypophosphatasia have been treated with blood plasma
transfusions to supplement the deficient enzyme alkaline phosphatase.
However, more research is needed before this treatment can be used for more
than the most severe cases of Hypophosphatasia.

This disease entry is based upon medical information available through
April 1990.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Hypophosphatasia, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Dr. Michael P. Whyte
     Medical Director, Metabolic Research Unit
     2001 S. Lindbergh Blvd.
     St. Louis, MO  63131-3597
     [phone], ext. 278

     The National Arthritis and Musculoskeletal and Skin Diseases Information
Clearinghouse
     Box AMS
     Bethesda, MD  20892
     [phone]

     Research Trust for Metabolic Diseases in Children
     Golden Gates Lodge, Weston Rd.
     Crewe CW1 1XN, England
     Telephone:  [phone]

For genetic information and genetic counseling referrals, please contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.:  John B. Stanbury, et al.,
eds; McGraw Hill, 1983.  Pp. 1497-1507.

INFANTILE HYPOPHOSPHATASIA:  ENZYME REPLACEMENT THERAPY BY INTRAVENOUS
INFUSION OF ALKALINE PHOSPHATASE-RICH PLASMA FROM PATIENTS WITH PAGET BONE
DISEASE:  M.P. Whyte, et al.; Journal Pediatr (September 1982:  issue 101(3)).
Pp. 379-386.

ENZYME REPLACEMENT THERAPY FOR INFANTILE HYPOPHOSPHATASIA ATTEMPTED BY
INTRAVENOUS INFUSIONS OF ALKALINE PHOSPHATASE-RICH PAGET PLASMA:  RESULTS IN
THREE ADDITIONAL PATIENTS:  M.P. Whyte, et al.; Journal Pediatr (December
1984:  issue 105(6)).  Pp. 926-933.

INFANTILE HYPOPHOSPHATASIA DIAGNOSED AT 4 MONTHS AND SURVIVING AT 2
YEARS:  A. Albeggiani, et al.; Helv Paediatr Acta (1982:  issue 37(1)).  Pp.
49-58.