Pseudohypoparathyroidism type 1A

Alternate names

PHP1A; Albright hereditary osteodystrophy with multiple hormone resistance

Definition

Pseudohypoparathyroidism type 1A is a type of pseudohypoparathyroidism. Pseudohypoparathyroidism is when your body is unable to respond to parathyroid hormone, which is a hormone that controls the levels of calcium, phosphorous, and vitamin D in the blood.

Cause

Pseudohypoparathyroidism type 1A is caused by a spelling mistake (mutation) in the GNAS gene.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

It is inherited in an autosomal dominant manner.

Signs and symptoms

• The symptoms are very similar to hypoparathyroidism (when parathyroid hormone levels are too low).
• The main symptoms are low calcium levels and high phosphate levels in the blood.
• This results in cataracts, dental problems, seizures, numbness, and tetany (muscle twitches and hand and foot spasms).
• Symptoms are generally first seen in childhood.
• People with this disorder are also resistant to other hormones, such as thyroid-stimulating hormone and gonadotropins.
• Type 1A is also associated with a group of symptoms referred to as Albright's hereditary osteodystrophy, which includes short stature, a round face, obesity, and short hand bones.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

100% of people have these symptoms

• Pseudohypoparathyroidism

80%-99% of people have these symptoms

• Elevated circulating parathyroid hormone level
• Hyperphosphatemia(High blood phosphate levels)
• Low urinary cyclic AMP response to PTH administration
• Pituitary resistance to thyroid hormone
• Round face(Circular face)
• Short stature(Decreased body height)

30%-79% of people have these symptoms

• Basal ganglia calcification
• Brachydactyly(Short fingers or toes)
• Broad 1st metacarpal(Wide 1st long bone of hand)
• Cataract(Clouding of the lens of the eye)
• Choroid plexus calcification
• Constrictive median neuropathy
• Delayed eruption of teeth(Delayed eruption)
• Depressed nasal bridge(Depressed bridge of nose)
• Ectopic ossification
• Full cheeks(Apple cheeks)
• Growth hormone deficiency
• Hypoplasia of dental enamel(Underdeveloped teeth enamel)
• Increased bone mineral density(Increased bone density)
• Intellectual disability(Mental deficiency)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Obesity (Having too much body fat)
• Polyphagia(Voracious appetite)
• Short 4th metacarpal(Shortened 4th long bone of hand)
• Short 5th metacarpal(Shortened 5th long bone of hand)
• Short fifth metatarsal(Short 5th long bone of foot)
• Short neck(Decreased length of neck)
• Thickened calvaria(Increased thickness of skull cap)

Diagnosis

• Serum calcium, phosphorus, and parathyroid hormone levels should be checked together as well as 25OH Vitamin D levels.
• The presence of hypocalcemia, hyperphosphatemia, normal 25 hydroxyvitamin D and elevated parathyroid hormone levels suggest pseudohypoparathyroidism. Synthetic PTH challenge test can be performed (Ellsworth-Howard test) but is not necessary for diagnosis.
• An electrocardiogram is likely appropriate if significant hypocalcemia is present to assess for prolonged QT interval and risk for arrhythmia.
• PHP1 patients should have biochemical testing completed annually, including PTH, calcium, phosphate, TSH, and urine calcium.
• Monitoring of appropriate height and growth is important, and testing for growth hormone deficiency should take place even if the height is normal.
• Screening and treatment for other endocrinopathies such as hypogonadism should be individualized.
• X-rays of upper and lower extremities to screen for brachydactyly are recommended during the initial evaluation.
• In patients with PHP with AHO, genetic testing is essential. Genetic testing and counseling provide information regarding likely disease manifestations and future complications. Additionally, genetic testing can help determine inheritance patterns within families and provide insight into the possibility of affected offspring.

Treatment

• The overall goals in the treatment of PHP are to maintain normal calcium, normal phosphorus, avoid hypercalciuria, and lower PTH levels to normal if possible.
• It is typically not possible to achieve all electrolyte and hormone level goals; however, getting them as close as possible is recommended.

NIH genetic and rare disease info

• NIH info on Pseudohypoparathyroidism type 1A

Pseudohypoparathyroidism type 1A is a rare disease.

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