Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

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2 is challenging; high doses of cholecalciferol (5000–40,000 U/day), calcitriol

(17–20 μg /day), and oral calcium therapy have been tried with varying success.

In case of failure with these regimens, therapy with intravenous calcium is indi-

cated. This not only results in normalization of serum calcium, but also in heal-

ing of rickets. Therapy with intravenous calcium leads to correction of

hypocalcemia and secondary hyperparathyroidism, thereby resulting in

improvement in serum phosphorus and healing of rachitic lesions in patients

with VDDR type 2, even without vitamin D or phosphorus therapy. Intravenous

calcium therapy can be given on a continuous or intermittent basis and can be

stopped once the growth of child is complete.

64. What are the familial disorders of phosphate homeostasis?

The familial disorders of phosphate homeostasis are due to mutation of genes

involved in phosphatonin secretion and degradation, or renal phosphate trans-

porters. They are enlisted in the table given below.

Disease Gene defect Remarks

X-linked hypophosphatemic

rickets

Loss-of-function mutation of

PHEX gene

Decreased cleavage

of FGF-23

Autosomal dominant

hypophosphatemic rickets

Gain-of-function mutation of

FGF-23 gene

Proteolysis-resistant

FGF-23

Autosomal recessive

hypophosphatemic rickets

Loss-of-function mutation of

DMP1, EMPP1

Increased FGF-23

Hereditary hypophosphatemic

rickets with hypercalciuria

Loss-of-function mutation of

NaPi 2c

Phosphaturia

Tumoral calcinosis Gain-of-function mutation of

GALNT3

Associated with
hyperphosphatemia
Loss-of-function mutation of
FGF-23 or Klotho
PHEX phosphate-regulating endopeptidase homolog, X linked, DMP1 dentin matrix protein-1,
EMPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1, GALNT3 polypeptide
N-acetylgalactosaminyltransferase 3

65. What are the characteristic manifestations of X-linked hypophosphatemic
    rickets–osteomalacia?
    Children with X-linked hypophosphatemic rickets/osteomalacia (XLH) usually
    present between 2 and 3 years of age with bowing of legs and short stature.
    Upper limb deformities are uncommon as the disease does not manifest during
    crawling stage of life. Dental abscess and enthesopathy are other characteristic
    abnormalities present in these patients. Poorly mineralized dentine provides an
    easy access to microbes to the pulp of teeth, thereby resulting in dental abscess.
    The cause of enthesopathy in patients with XLH is not clear; however, FGF-23
    has been implicated. The biochemical characteristics of XLH include hypo-
    phosphatemia, normocalcemia, normal to mildly elevated PTH and alkaline

5 Rickets–Osteomalacia