OVERVIEW

What is Pseudopseudohypoparathyroidism (PPHP)?

Pseudopseudohypoparathyroidism, abbreviated as PPHP, is a relatively rare monogenic inherited disorder.

Patients with PPHP exhibit physical features similar to those of pseudohypoparathyroidism (PHP), including characteristic traits such as a round face, short stature, shortened fourth metacarpal bones, obesity, subcutaneous calcifications, and developmental delays (i.e., Albright hereditary osteodystrophy).

However, PPHP differs significantly from typical PHP in biochemical aspects. In PHP, parathyroid hormone fails to function properly, leading to manifestations of hypoparathyroidism, whereas in PPHP, the kidneys retain responsiveness to parathyroid hormone, so symptoms of hypoparathyroidism (hypocalcemia, hyperphosphatemia) are less apparent. Thus, some consider PPHP a variant of PHP type Ia.

PPHP cannot be cured and requires long-term treatment with regular follow-ups.

Is Pseudopseudohypoparathyroidism (PPHP) common?

PPHP is a rare genetic disorder.

Are Pseudopseudohypoparathyroidism (PPHP) and Pseudohypoparathyroidism (PHP) the same disease?

No, they are not the same disease.

Pseudohypoparathyroidism (PHP) refers to a group of disorders where target organs (kidneys and bones) fail to respond to parathyroid hormone, meaning PHP is not a single disease but a collective term for multiple conditions.

Genetically, PPHP and PHP type Ia result from mutations in the same gene. The difference lies in the parental origin of the mutation—one from the father and the other from the mother—leading to distinct clinical manifestations due to differences in genomic imprinting.

Patients with PHP type Ia exhibit unresponsiveness to parathyroid hormone in both kidneys and bones, resulting in skeletal abnormalities along with hypocalcemia and hyperphosphatemia. In contrast, PPHP patients show poor skeletal response but retain renal responsiveness to PTH, so they only display osteodystrophy without calcium or phosphate abnormalities.

SYMPTOMS

What are the common manifestations of Pseudopseudohypoparathyroidism (PPHP)?

• Albright hereditary osteodystrophy (AHO): Characterized by intellectual disability, stocky short stature, early-onset obesity, round face, short neck, brachydactyly (short fingers/toes), and common shortening of the 1st, 4th, and 5th metacarpals or metatarsals, leading to dimpling over these knuckles when making a fist (Albright's sign).
• May be accompanied by taste/smell disorders and associated with hypothyroidism, adrenal insufficiency, diabetes insipidus, or gonadal dysgenesis/underdevelopment.

CAUSES

What is the cause of pseudopseudohypoparathyroidism (PPHP)?

PPHP is a genetic disorder caused by gene defects.

Is pseudopseudohypoparathyroidism (PPHP) contagious?

No, it is not contagious.

Is pseudopseudohypoparathyroidism (PPHP) hereditary?

Yes, PPHP is a monogenic inherited disorder that can follow autosomal dominant or recessive inheritance patterns, often accompanied by various types of congenital malformations and defects.

DIAGNOSIS

How is Pseudopseudohypoparathyroidism (PPHP) diagnosed?

When diagnosing PPHP, doctors primarily rely on the presence of Albright hereditary osteodystrophy (AHO) but the absence of corresponding biochemical and metabolic abnormalities, meaning no significant hypocalcemia or hyperphosphatemia. Genetic sequencing to identify defective gene loci further aids in confirming the diagnosis.

What tests are needed to diagnose Pseudopseudohypoparathyroidism (PPHP)?

• Blood and urine tests: Normal parathyroid hormone levels, normal blood calcium and phosphorus levels, and normal urinary calcium and phosphorus excretion.
• Imaging studies: X-rays may reveal shortened metacarpals and phalanges, a common and early detectable feature of the disease, particularly affecting the 4th and 5th metacarpals and the distal phalanx of the thumb.
• Genetic sequencing: Helps identify defective gene loci, supporting the diagnosis.

Which diseases can Pseudopseudohypoparathyroidism (PPHP) be confused with, and how to differentiate them?

When diagnosing PPHP, it should be distinguished from the following conditions:

• Dwarfism: Features include growth retardation and short stature, but with normal intelligence, reduced growth hormone levels, and absence of tetany or AHO signs, distinguishing it from PPHP.
• Cretinism: Characterized by short stature, intellectual disability, elevated thyroid-stimulating hormone levels, and absence of tetany or AHO signs, differentiating it from PPHP.

TREATMENT

Which department should I visit for pseudopseudohypoparathyroidism (PPHP)?

Endocrinology.

Can pseudopseudohypoparathyroidism (PPHP) heal on its own?

No, it cannot heal on its own and cannot be cured. Long-term treatment and regular follow-ups are required.

How is pseudopseudohypoparathyroidism (PPHP) treated?

PPHP may be accompanied by various endocrine disorders, such as hypothyroidism, adrenal insufficiency, diabetes insipidus, or gonadal dysgenesis. Treatment should target the specific endocrine abnormalities.

• If the patient has hypothyroidism, thyroid hormone replacement therapy may be given.
• If the patient has delayed sexual development or reduced menstrual flow, sex hormone replacement therapy may be administered.

Additionally, since patients often have short stature, a growth hormone stimulation test should be performed early, and growth hormone therapy should be initiated as needed (before puberty).

Does pseudopseudohypoparathyroidism (PPHP) require hospitalization?

Hospitalization is generally not required.

DIET & LIFESTYLE

Does Pseudopseudohypoparathyroidism (PPHP) require re-examination? How to re-examine?

Pseudopseudohypoparathyroidism requires re-examination. Follow-up should be conducted as required based on concurrent endocrine diseases and medication treatment. Specific details can be referred to in the corresponding disease entries.

PREVENTION

Can Pseudopseudohypoparathyroidism (PPHP) be prevented? How to prevent it?

Pseudopseudohypoparathyroidism is a type of genetic disorder, so the prevention of this disease mainly relies on prenatal diagnosis.

For individuals carrying gene mutations, prenatal diagnosis is crucial, as it can prevent the birth of affected individuals.