Albright hereditary osteodystrophy with hypothyroidism, normocalcemia, and normal Gs protein activity: a family presenting with congenital osteoma cutis.
The syndrome of Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) is clinically and genetically heterogeneous. Classically, patients with PHP have the skeletal features of AHO, resistance to multiple hormones that work via cAMP such as parathyroid hormone and thyroid stimulating hormone, and deficient activity of Gs protein, the guanine nucleotide-binding protein that stimulates adenylate cyclase. However, patients without hormone resistance but with AHO and Gs deficiency were described (PPHP), as well as patients with multiple hormone resistance but without AHO or Gs deficiency. In a few patients with deficient Gs activity, hypothyroidism rather than hypocalcemia was the initial presentation of the disorder. We describe here a new variant of the syndrome, affecting 5 individuals in a 3 generation family with AHO, normal Gs activity and hypothyroidism. In the first 2 generations, mild features of AHO were present. The 2 sibs in the third generation had severe manifestations of AHO, including mild mental retardation as well as hypothyroidism. Diagnosis of congenital osteoma cutis at birth of the proband led to the diagnosis of the family. Elucidation of the molecular defect will shed light on the relationship between hormone resistance and AHO, as well as on the physiological mechanism of hormonal signal transduction.
Izraeli
S
S
Department of Pediatrics, Beilinson Medical Center, Petach Tiqva, Israel.
Metzker
A
A
Horev
G
G
Karmi
D
D
Merlob
P
P
Farfel
Z
Z
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010016:Osteoma / Q000097:blood / Q000235:genetics*; D010375:Pedigree; D011547:Pseudohypoparathyroidism / Q000097:blood / Q000150:complications / Q000235:genetics*; D012016:Reference Values; D012878:Skin Neoplasms / Q000097:blood / Q000235:genetics*; D013577:Syndrome
D019204:GTP-Binding Proteins