I l. Rickets-like diseases. Hypophosphatemic rickets. Hypervitaminosis D. Flashcards
causes of hypophosphatemic rickets ? L
phosphopenic
Most commonly hypophosphatemic rickets is due to changes in the PHEX gene and inherited in an X-linked dominant manner (X-linke d hypophosphatemia).
increased levels of fibroblast growth factor 23 (FGF23)
impaired reabsorption o ‘ f phosphate → chronic hypophosphatemia → vitamin D-resistant rickets
Fibroblast growth factor 23 normally inhibits the kidneys’ ability to reabsorb phosphate into the bloodstream
autosomal dominant / recessive hypophophatemic rickets
Less commonly it is inherited in an X-linked recessive manner (often called Dent disease
these genes directly or indirectly regulate a protein that normally inhibits the kidneys’ ability to reabsorb phosphate into the blood.
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Hereditary hypophosphotemic rockets with hypercalciurea
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Fanconisyndrome metabolic bone disease is not always present.
accompanied by metabolic acidosis secondary to proximal tubular bicarbonate wasting (type II renal tubular acidosis)
- excretion in the urine
potassium, glucose, phosphate,
vit d resistant hypophosphotemic rickets
Short stature
Polyuria → polydipsia, dehydration
In some cases, features of hypokalemia (e.g., muscle weakness, hyporeflexia, paralysis
symptoms of hypophosphatemic rickets ?
begin in infancy or early childhood
x linked hypophosphatemia Age of symptom onset: typically < 3 years
bowing of the legs
bone pain
joint pain
short stature.
premature closure of the skull bones in babies (craniosynostosis);
limited joint movement;
and dental abnormalities
Unlike vitamin D deficiency, craniotabes and rachitic rosary are not common
x linked dominant
initial clinical findings is frontal bossing, which may appear as early as 6 months of age
cerebellar tonsillar protrusion (Chiari type 1 malformation l
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Autosomal Dominant Hypophosphatemic Rickets
variable age of onset and an incomplete penetrance
2 subgroups
One presents during childhood and mimics X-linked dominant hypophosphatemic rickets.
The other subgroup presents during adolescence or adulthood with bone pain, weakness, and pseudo fractures but no deformity
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Autosomal Recessive Hypophosphatemic Rickets
similar to those with X-linked dominant hypophosphatemic rickets
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Hereditary Hypophosphatemic Rickets With Hypercalciuria
dental abnormalities not reported
diagnosis of hypophosphatemic rickets ?
Laboratory tests
phophopenic
calcium - neutral phosphate - very low alkaline phosphatase - high PTH - neutral decreased or normal - active vit d
fanconi - phosphate - low calcium - normal alkaline phosphatase - elevated PTH - NORMAL active vit d - low
x linked dominant /Autosomal Dominant Hypophosphatemic Rickets / Autosomal Recessive Hypophosphatemic Rickets
Increased FGF-23
Hereditary Hypophosphatemic Rickets With Hypercalciuria
not elevated FGF -23
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urinary wasting of AAs, glucose, phosphate, uric acid, bicarbonate and other solutes is found, the diagnosis of complete FS is made
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and diagnostics for osteomalacia and rickets
treatment of hypophosphatemic rickets?
phosphate - by mouth in effervescent tablets l
For Child 1 month–4 years
2–3 mmol/kg daily
For Child 5–17 years
2–3 mmol/kg daily
can also be IV
For Neonate
1 mmol/kg
For Child 1 month–1 year
0.7 mmol/kg daily,
Child 2–17 years
0.4 mmol/kg daily
benefit from calcitriol supplementation (20–30 ng/kg per day)
In the management of X-linked hypophosphatemia secondary hyperparathyroidism results from the persistent stimulation of parathyroid cells by FGF-23 and phosphate supplements
cinacalcet, for persistent secondary hyperparathyroidism if higher dosage of active vitamin D and/or lower dosage of oral phosphate fail to normalize PTH levels
extreme caution should be exercised while using cinacalcet because of severe side effects, such as hypocalcemia and prolonged QT interval
recent development is the introduction of burosumab (KRN23), a human monoclonal antibody against FGF-23 that has been shown to be effective in children with X-linked hypophosphatemia
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evaluation and treatment l of iron deficiency is important in children with autosomal dominant hypophosphatemic rickets, as iron deficiency causes increased expression of the FGF-23 gene.
what causes hypervitaminosis d ?
occurs when you take in too much vitamin D
Granulomatous disorders (e.g., sarcoidosis): due to increased 1α-hydroxylase activation in epithelioid macrophages → increased 1,25-dihydroxyvitamin D synthesis
Estrogen therapy, taking antacids for a long time, and isoniazid an antituberculosis medication l
what are the side effects of hypervitaminosis D ?
abnormally high levels of calcium in the blood.
clinical features of hypervitaminosis d ?
, hypercalciuria
kidney stones
Bone pain, arthralgias, myalgias,
Constipation
Abdominal pain
Peptic ulcer disease [10]
Pancreatitis
Neuropsychiatric symptoms such as anxiety, depression, fatigue, and cognitive dysfunction
Somnolence
Diminished muscle excitability
Cardiac arrhythmias
Muscle weakness, paresis
Polyuria an
Diagnosis of hypervitaminosis d
blood tests to check vitamin D levels, calcium, and phosphorus
urine tests to check for excessive amounts of calcium in the urine
bone X-rays to determine if there’s significant bone loss
where is vit d2 and vit d3 found ?
vitamin D2 (ergocalciferol) - naturally through the conversion of dehydrocholesterol to cholecalciferol in the skin by sunlight (ultraviolet B
pathophysiology of phosphate and calcium ?
phosphate binds to calcium - causing it to decrease
hypophosphatemia
increased calcium
decreased pth
decreased active vit d
Deficient bone mineralization is due to low phosphate levels and osteoblast dysfunction rather than to the low calcium and elevated parathyroid hormone (PTH) levels as in calcipenic rickets. Because 1,25-dihydroxyvitamin D3 levels are normal to slightly low,
hypophosphatemia would normally cause elevated 1,25-dihydroxyvitamin D3 levels
