Transcript Familial hypophosphatemic Rickets

Rickets
Definition of Rickets
Rickets, a disease of growing bone,
occurs in children only before fusion
of the epiphyses, and is due to
unmineralized matrix at the growth
plates.
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• Proper bone formation requires a complex
interplay of several organs and chemicals and
vitamin D deserves special mention because
any disturbance in its production, absorption,
or metabolism is paramount in the
development of rickets.
• Human beings maintain adequate levels of
vitamin D by producing it from cholesterol or
by absorbing it from ingested food sources.
• Sunlight is a vital component necessary for
the production of vitamin D, which begins in
the skin and ends in the kidney .
thway of Vitamin D Production
Functions of Chemicals Involved in
Bone Formation:
• Alkaline phosphatase:
Exact function unknown; isoenzyme is
elevated in conditions such as rickets that are
associated with high bone turnover.
Functions of Chemicals Involved in
Bone Formation:
• Calcitriol:
Bone: indirectly stimulates bone synthesis
via increased calcium absorption in intestinal
lumen.
Intestine: increases calcium, phosphorus, and
magnesium absorption.
Kidney: autoregulation of calcitriol
production by the kidney.
Parathyroid gland: negative feedback to
decrease secretion of parathyroid hormone.
Functions of Chemicals Involved in
Bone Formation:
• Parathyroid hormone:
Bone: mobilizes calcium and phosphorus.
Intestine: indirectly increases calcium and
phosphorus absorption by increasing
calcitriol.
Kidney: increases 1,25OHvit D, increases
calcium reabsorption, decreases phosphorus
reabsorption.
‫يافته های آزمايشگاهی‬
‫‪PTH‬‬
‫‪CAMpu‬‬
‫‪ 1,25‬آلکالن‬
‫‪ (OH)2‬فسفات‬
‫‪ D3‬از‬
‫آمينو‬
‫اسيد‬
‫ادرار‬
‫مرحله‬
‫اول‬
‫↓‬
‫‪N‬‬
‫‪N‬‬
‫↑‪or‬‬
‫‪N‬‬
‫‪N‬‬
‫‪N‬‬
‫‪N‬‬
‫مرحله‬
‫دوم‬
‫مرحله‬
‫سوم‬
‫‪N‬‬
‫↓‬
‫↑‬
‫↑‬
‫↑‬
‫↑‬
‫↑‬
‫↓‬
‫↓‬
‫↑‬
‫↑‬
‫↑‬
‫↑‬
‫↑‬
‫‪p ca‬‬
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‫‪Radiological findings:‬‬
‫‪ Widening ,Fraying, Cupping -1‬صفحه رشداپی فيزی‬
‫‪ -2‬کاهش مينراليزاسيون صفحه رشد‬
‫‪ Translucent gap -3‬بين اپی فيز و متافيز‬
‫‪ -4‬ظهور اپی فيز به تاخير می افتد‪ ،‬اپی فيزکوچک‬
‫‪ Cupping -5‬و ‪ Widening‬متافيزباعث می شود که نسج نرم انتهای‬
‫استخوان‪Expansion‬پيدا کند و برجسته و متورم به نظر‬
‫برسد‪ ،)Rickets Rosary(.‬پهن شدن مچ دست و قوزک‪.‬‬
‫‪ -6‬کورتکس نازک‬
‫‪ -7‬استئوپنی‬
‫‪ -8‬ترابکولهای استخوانی کم و خشن‬
CLINICAL MANIFESTATIONS :
• Delay in the closure of the fontanelles
• Parietal and frontal bossing (caput
quadratum)
• Craniotabes (soft skull bones)
• Rachitic rosary
• Harrison sulcus
• Enlargement of the wrist and bowing of the
distal radius and ulna
• Progressive lateral bowing of the femur and
tibia
CLINICAL MANIFESTATIONS :
• Hypoplasia of the dental enamel .
• Decreased muscle tone, leading to delayed
achievement of motor milestones .
• Hypocalcemic seizures (frequent presenting
sign in the first year of life ) .
• Prone to acquiring infectious diseases .
• Increased sweating is a common finding in
young infants .
Skeletal and Radiographic Findings
Associated with Rickets:
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Flaring of wrists .
Fractures.
Fraying and cupping of metaphysis .
Frontal bossing of skull .
Genu valgum or varum.
Lordosis/kyphosis/scoliosis .
Osteopenia
Types of Rickets:
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Nutritional rickets
Vitamin D-dependent rickets
Familial hypophosphatemic rickets
Hereditary hypophosphatemic rickets with
hypercalciuria
• Other causes of rickets include renal disease,
medications, and malabsorption syndromes.
Nutritional Rickets:
• Nutritional rickets results from inadequate
sunlight exposure or inadequate intake of
dietary vitamin D, calcium, or phosphorus .
• Vitamin D deficiency can occur when an
infant is solely breastfed, is dark skinned, or
has limited sunlight exposure .
• Breast milk content of vit D: 12 – 60 IU/lit
Nutritional Rickets:
• Nutritional rickets presents in the first two
years of life with short stature, gait
abnormality, developmental delay, and
characteristic findings.
• Commonly, infants younger than six months
present with hypocalcemic tetany or seizures,
whereas older children present with failure
to thrive or skeletal deformities .
VITAMIN D–DEPENDENT RICKETS,
TYPE 1:
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Autosomal recessive
Mutation in gene of renal 1α-hydroxylase
They present during the 1st 2 yr of life.
Biochemical finding :
25-D …. normal
1,25-D…. decreased
PTH…. increased
Ph…. decreased
ca…. decreased
metabolic acidosis
 The only form of richets with hypocalcemia.
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VITAMIN D–DEPENDENT RICKETS,
TYPE 2:
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Autosomal recessive
Mutation in gene of vitamin D receptor.
Levels of 1,25-D are extremely elevated
Approximately 50–70% of children have
alopecia(areata or totalis).
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X-LINKED HYPOPHOSPHATEMIC
RICKETS:
• Pathophysiology:
The defective gene is called PHEX.
This gene have a role in inactivating
phosphatonin.
increased phosphate excretion.
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• Hypophosphatemia also can occur secondary
to hereditary hypophosphatemic rickets with
hypercalciuria, which is believed to result
from an isolated defect in renal reabsorption
of phosphorus .
Other Causes:
Medications:
Antacids
Anticonvulsants
Corticosteroids
Loop diuretics
 Malignancy
Prematurity
Tumor-induced osteomalacia:
This is more common in adults.
In children, it produce classic rachitic
findings.
The tumors are benign, small, and located in
bone.
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Other Causes:
• Diseases of organs associated with vitamin D
and calcium metabolism :
Kidney disease
Liver and biliary tract disease
• Malabsorption syndromes :
Celiac disease
Cystic fibrosis (rare)
• Premature infants are at risk of
developing rickets from calcium and
phosphorus deficiency and side effects
of their medications (e.g., loop diuretics,
corticosteroids) .
Evaluation
MEDICAL HISTORY:
• The infant's gestational age, diet, and degree
of sunlight exposure should be noted .
• A detailed dietary history should include
specifics of vitamin D and calcium intake .
• A family history of short stature, orthopedic
abnormalities, poor dentition, alopecia, and
parental consanguinity may signify inherited
rickets .
MEDICAL HISTORY:
• Researchers have suggested an appropriate
amount of sunlight exposure for infants (i.e.,
30 minutes per week if only in a diaper and
two hours per week if fully clothed), but the
exact amount needed for a particular child is
not known .
(J Pediatr 1985;107:372-6 )
Physical Examination:
• In children with rickets, complete physical and
dental examinations should be performed .
• The entire skeletal system must be palpated to
search for tenderness and bony abnormalities .
• Bowlegs in the absence of other findings are
relatively common in normal children in the first
two years of life.
Treatment
Nutritional Rickets:
• Treatment:
vitamin D
nutritional intake of ca
There are 2 strategies for administration of vitamin D:
a)In first year
100,000-200,000 IU vit D orally or
im
b)After 1 year
300,000–600,000 IU vit D orally o
im
alternative :
4–6 wk.
2,000–5,000 IU/day over
‫تغييرات بيوشيميايی پس ازدرمان‪:‬‬
‫‪ ଈ‬کلسيم درعرض ‪ 3‬روزنرمال می شود‪.‬‬
‫‪ ଈ‬فسفرآخرهفته اول نرمال می شود‪.‬‬
‫‪ ଈ‬آلکالن فسفاتازچندين هفته تا ماه باال باقی می ماند ‪ ،‬به طور‬
‫معمول ‪ 6‬تا ‪ 12‬ماه بعد کاهش می يابد‪.‬‬
‫‪ ଈ‬بهبودی عالئم راديولوژی ‪ 2‬هفته ديرتراز تغييرات بيوشيميايی رخ‬
‫می دهد‪.‬‬
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Vitamin D-dependent Rickets:
• Because vitamin D-dependent rickets, type I
is caused by lack of production of calcitriol,
treatment requires the replacement of that
active product. (calcitriol:0.25-2μg/day)
Treatment:
The treatment of type II is more complex
1)high-dose vitamin D(vitamin D2, 25-D, or 1,25-D)
50-60 μg/day 1,25-D
2)oral calcium (1–3 gr/day)
• If do not respond to high-dose vitamin D :
long-term Iv calcium, with transition to very high-dose oral
calcium.
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Familial hypophosphatemic Rickets:
• Familial hypophosphatemic rickets is treated
with oral phosphorus and calcitriol (Rocaltrol).
• Hereditary hypophosphatemic rickets with
hypercalciuria requires replacement of oral
phosphorus alone.
• Joulie's solution (155 g of dibasic anhydrous
sodium phosphate and 64 g of phosphoric acid
85 percent per liter solution, corresponding to
50 mg/mL of elemental phosphorus).
Treatment:
• oral phosphorus (1–3 g of elemental
phosphorus divided into 4–5 doses ) &
• 1,25-D (calcitriol 30–70 ng/kg/day divided
into 2 doses ).
• growth hormone (significant short stature)
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Rickets associated with
anticonvulsants:
• Needs 1000 and sometimes 4000 IU /day vit D.
Oncogenic rickets:
• excision of the tumor.
If cannot be removed, treatment is identical
to that used for XLH.
KEY RECOMMENDATIONS FOR PRACTICE:
• Surgical intervention may be necessary to
repair severe bony abnormalities in children
with rickets, but it should not be undertaken
until the biochemical derangements have
resolved so that optimal healing occurs at the
surgical site .
Differential Diagnosis
Metaphyseal dysplasia:
• Bowing of legs.
• Short stature.
• Waddling gait.
• Normal level of Ca,Ph,alkaline phosphatase.
• Cupped or ragged metaphyses.
• Jansen type & Schmid type.
Differential Diagnosis:
Hypophosphatasia :
• X-ray resembles rickets.
• Low level of alkaline phosphatase.