Albright's Hereditary Osteodystrophy (AHO) is a rare Genetic Disorder marked by distinctive skeletal and developmental features. It stems from cellular resistance to certain hormones, particularly Parathyroid Hormone, disrupting Calcium and Phosphate balance in the body.
Causes
AHO is typically caused by mutations in the GNAS Gene, which encodes a protein involved in Signal Transduction within cells. It is inherited in an Autosomal Dominant pattern, though the clinical presentation can vary depending on which parent the affected gene is inherited from (parental imprinting). The mutation leads to reduced activity of G-proteins, crucial for Hormone signaling. This reduction in activity causes target tissues to become resistant to the effects of various hormones, not just PTH.
Symptoms
The clinical presentation of AHO is diverse, but common features include short stature, a round face, and Obesity. Characteristic skeletal abnormalities often include brachydactyly (shortening of metacarpal and metatarsal bones), leading to dimples over the knuckles or toes. Subcutaneous Calcification and Ossification (bone formation in soft tissues) are also frequently observed. Some individuals may experience varying degrees of Intellectual Disability. When this genetic condition is accompanied by Hormone Resistance to Parathyroid Hormone, leading to Hypocalcemia and Hyperphosphatemia, it is known as Pseudohypoparathyroidism Type 1a. Resistance to other hormones, such as Thyroid Stimulating Hormone (leading to Hypothyroidism) or Gonadotropins, can also occur.
Diagnosis and Treatment
Diagnosis typically involves a combination of clinical assessment of characteristic features, biochemical tests to evaluate Calcium and Phosphate levels, and Genetic Testing for GNAS mutations. Treatment is primarily symptomatic and supportive, focusing on managing the hormonal imbalances and associated complications. This often includes oral Calcium and Vitamin D supplementation to correct hypocalcemia and manage parathyroid hormone resistance. Other endocrine deficiencies, such as hypothyroidism, are treated with appropriate hormone replacement therapies.
