Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Albright hereditary osteodystrophy

The disease is cause by mutations or imprinting defects in the GNAS1 gene. The syndrome is characterized by pseudohypoparathyroidism and skeletal abnormalities associated sometimes with mental retardation.

Clinical Findings

The clinical symptoms of Albright hereditary osteodystrophy (AHO) include pseudohypoparathyroidism (PHP) (renal parathyroid hormone resistance) and disturbances of skeletal development (short stature, obesity, round face, intramembranous ossifications, brachydactyly, and other). PTH resistance accounts for hypocalcemia and hyperphosphatemia which is not amenable to PTH treatment.

The imprinting mechanism of this gene brings about that the disease occurs only when it is passed by a mother with mild clinical symptoms or a de novo mutation of the maternal allele. If the mutation is paternally inherited the symptoms are usually milder and the laboratory findings (calcium and phosphate) are normal. This condition is named pseudopseudohypoparathyroidism (PPHP).

Symptoms

Heterotopic Ossification
In Albright hereditary osteodystrophy (AHO) subcutaneous ossifications are accompanied by hormone resistance and dysmorphic features.

Systematic

Hereditary bone disease
Acro-renal-ocular syndrome
Albright hereditary osteodystrophy
GNAS
Bone dysplasia
Ehlers-Danlos syndrome due to tenascin-X deficiency
IVIC syndrome
Kabuki syndrome
Metabolic bone disease
Osteoarthritis susceptibility 5

References:

1.

Spiegel AM et al. (1999) Hormone resistance caused by mutations in G proteins and G protein-coupled receptors.

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2.

Simon A et al. (2000) Pseudohypoparathyroidism type Ia. Albright hereditary osteodystrophy: a model for research on G protein-coupled receptors and genomic imprinting.

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3.

Spiegel AM et al. (2000) G protein defects in signal transduction.

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4.

Aldred MA et al. (2000) Activating and inactivating mutations in the human GNAS1 gene.

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5.

Kaplan FS et al. (2000) Progressive osseous heteroplasia.

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6.

Weinstein LS et al. (2001) Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting.

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7.

Lania A et al. (2001) G protein mutations in endocrine diseases.

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8.

Weinstein LS et al. (2002) Gs(alpha) mutations and imprinting defects in human disease.

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9.

Butler MG et al. (2002) Imprinting disorders: non-Mendelian mechanisms affecting growth.

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10.

Jabbour SA et al. (2003) Cutaneous manifestations of endocrine disorders: a guide for dermatologists.

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11.

Levine MA et al. (2003) Genetic basis for resistance to parathyroid hormone.

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12.

Weinstein LS et al. (2004) Minireview: GNAS: normal and abnormal functions.

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13.

Spiegel AM et al. (1997) The molecular basis of disorders caused by defects in G proteins.

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14.

Spiegel AM et al. (1997) Inborn errors of signal transduction: mutations in G proteins and G protein-coupled receptors as a cause of disease.

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Update: Sept. 26, 2018