ALBRIGHT HEREDITARY OSTEODYSTROPHY; AHO #103580 Alternative titles; PSEUDOHYPOPARATHYROIDISM, TYPE IA, INCLUDED PHP IA, INCLUDED PHP1A, INCLUDED PSEUDOPSEUDOHYPOPARATHYROIDISM, INCLUDED; PPHP, INCLUDED PSEUDOHYPOPARATHYROIDISM, TYPE IC, INCLUDED PHP IC, INCLUDED Pseudohypoparathyroidism is a term applied to a heterogeneous group of disorders whose common feature is resistance to parathyroid hormone (PTH; 168450). It is generally classified as types Ia, Ib (603233), Ic, and II (203330) according to different phenotypes and pathogenesis. Albright hereditary osteodystrophy (AHO) is a syndrome characterized by several distinct physical features, including short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation. AHO is often associated with pseudohypoparathyoidism, hypocalcemia, and elevated PTH levels (PHP Ia). Patients with pseudopseudohypoparathyroidism have normal calcium metabolism and PTH levels with isolated AHO (Kinard et al., 1979, Fitch, 1982).

A heritable syndrome featuring: hypocalcemia brachydactyly moderate dwarfing mental retardation soft tissue calcifications basal ganglia calcifications cataracts tetany hyperphosphatemia and hypocalcemia (PTH resistant) normal PTH levels

Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biological activity of PTH. Synonyms and related keywords: PHP, Albright hereditary osteodystrophy, AHO, pseudopseudohypoparathyroidism, pseudo-PHP, parathyroid hormone, PTH, stimulatory G protein, Gsa, GNAS1, hypocalcemia, hyperphosphatemia, testotoxicosis, dental hypoplasia, brachymetacarpals, brachymetatarsals, brachydactyly

3 synonyms or equivalents were found. Pseudohypoparathyroidism type 1a aka/or Seabright Bantam syndrome aka/or Albright's hereditary osteodystrophy Pseudohypoparathyroidism type 1a: Definition(s) via UMLS..... Pseudohypoparathyroidism: "A hereditary condition clinically resembling HYPOPARATHYROIDISM, but caused by failure of response to rather than deficiency of parathyroid hormones. It is characterized by hypocalcemia and hyperphosphatemia, and is commonly associated with short stature, obesity, short metacarpals, and ectopic calcification. (Dorland, 27th ed)" Source: Medical Subject Headings, 2007_2006_08_08 Pseudohypoparathyroidism: "hereditary condition clinically resembling hypoparathyroidism, but caused by failure of response to rather than deficiency of parathyroid hormones; characterized by hypocalcemia and hyperphosphatemia, and commonly associated with short stature, obesity, short metacarpals, and ectopic calcification." Source: CRISP Thesaurus, 2006 Pseudohypoparathyroidism: "Originally reported as a hypocalcemic syndrome similar to hypoparathyroidism, but with renal and skeletal resistance to parathyroid hormone (PTH) and designated as "pseudohypoparathyroidism." Albright later defined a normocalcemic variant which he termed "pseudopseudohypoparathyroidism." Two separate forms of pseudohypoparathyroidism are recognized. Type I in which there is no increase in the urinary excretion of cyclic adenosine monophosphate (cAMP) and phosphate in response to parathyroid hormone (PTH). Type II in which there is a response to PTH, but without phosphate diuresis. The erythrocytes of some patients with type I contain a defective receptor-cyclase coupling protein (stimulatory guanine nucleoside-binding protein, or GS) which is responsible for coupling the cellular receptor that binds parathyroid hormone (PTH) and is involved with the formation and release of cyclic adenosine monophosphate (cAMP). This variant has been designated as "pseudohypoparathyroidism type Ia." The syndrome is associated with mental deficiency, dystrophic bone lesions, short stature, and other defects." Source: Online Congenital Multiple Anomaly/Mental Retardation Syndromes, 1999 may cause or feature Miscellaneous syndromes Osteodystrophy Symptoms and Signs Anosmia Brachydactyly Corneal opacity Facies abnormality Infertility Obesity Rash Short stature Biochemical abnormalities Hyperphosphataemia Hypocalcaemia Hypogonadic hypogonadism X-ray abnormalities Ectopic calcification Endocrine conditions Hypothyroidism Psychiatric conditions Learning disability

Pseudohypoparathyroidism type 1b may cause or feature Biochemical abnormalities Hyperphosphataemia Hypocalcaemia

Discussion: - lack of responsiveness to PTH due to defect in adenyl cyclase; - clinical picture may resemble of hypoparathyroidism; - due to inability of bone & kidney to respond to parathyroid hormone, hypocalcemia and hyperphosphatemia occur in spite of elevated parathyroid levels; - pts w/ this disorder have a characteristic clinical appearance that includes short stature, round facies, & shortened 4th metacarpals; - subQ calcifications that may be present in pseudohypoparathyroidism not present in the idiopathic disorder;

Study of Growth Hormone Use in Pseudohypoparathyroidism Type 1a and Pseudopseudohypoparathyroidism This study is currently recruiting patients. Verified by FDA Office of Orphan Products Development September 2005 Sponsors and Collaborators: Food and Drug Administration (FDA) FDA Office of Orphan Products Development Thrasher Research Fund Johns Hopkins University