Calcium Homeostasis Disorders
CASR-Related Disorders of Calcium Homeostasis
Gene: CASR
Protein: calcium-sensing receptor
Clinical Characteristics
Familial Hypocalciuric Hypercalcemia Type I (FHH)
- Caused by inactivating mutations:
- Heterozygous mutation
- Mutation causes mild to moderate impairment of CASR function
- Mild to moderate hypercalcemia with relative hypocalciuria
- Normal serum parathyroid (PTH) levels
- May have hypermagnesemia and urine calcium/creatinine clearance ratio below 0.01
- Typically asymptomatic
- Individuals with moderate disease may have:
- Chondrocalcinosis
- Gallstones
- Kidney stones
- Pancreatitis
- Fatigue and weakness
- Polydipsia/polyuria
Neonatal Severe Hyperparathyroidism (NSHPT)
- Caused by inactivating mutations:
- Compound heterozygous or homozygous mutations
- Heterozygous mutations with a dominant negative effect (rare)
- Presents within first six months of life
- Severe symptomatic hypercalcemia with relative hypocalciuria
- Multiglandular parathyroid hyperplasia
- Bone demineralization resulting in rib cage deformities, rachitic changes and multiple fractures
- Failure to thrive, hypotonia, lethargy
- Severe neurodevelopmental defects if left untreated
Autosomal Dominant Hypocalcemia (ADH)/Familial Isolated Hypoparathyroidism (FIH)
- Caused by activating mutations (gain of function)
- Wide clinical spectrum
- May present with neonatal or childhood seizures secondary to fever and infection
- Hypocalcemia and hypercalciuria
- Normal to mildly elevated phosphate levels
- Low to normal parathyroid levels
- Increased risk for renal complications such as nephrocalcinosis, kidney stones or impaired renal function
Bartter Syndrome, Type V
- Caused by more severe activating mutations (gain of function)
- Hypocalcemia and hypercalciuria
- Renal salt wasting
- Hypokalemic metabolic alkalosis
- Elevated renin and aldosterone levels with low blood pressure
Inheritance Pattern
- Autosomal dominant for FHH, ADH, FIH, Bartter syndrome Type V
- Autosomal recessive for NSHPT
- Rarely autosomal dominant for NSHPT
What Can Be Learned From This Test
Testing is performed by sequencing the entire coding region of the CASR gene. This will detect point mutations, small deletions and small insertions. It will not detect a partial or whole gene deletion or duplication.
A negative test result does not rule out a diagnosis of a calcium homeostasis disorder. Other genes are known to be associated with some of these conditions, and this test will only detect mutations in CASR.
Sample Requirements
Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).
Turnaround time: 10-14 business days
CPT Codes and Cost
Full Gene Sequencing
- Code: 81405
- Cost: $950
Known Variant Testing
- Code: 81479
- Cost: $225