Summary
The case of a 41-year-old woman with cerebral calcification of a rather unusual extent is reported. This condition was associated with mental deficiency, pseudohypoparathyroidism and Albright's hereditary osteodystrophy. Four years later hypothyroidism was diagnosed. Visual impairment and electroretinogram abnormality suggested a retinopathy involving mostly rods. Despite their rarity, pseudohypoparathyroidism and Albright's hereditary osteodystrophy are of major interest, since they represent the only human disease states in which G protein function has been found to be disrupted. The overall clinical picture was strongly suggestive of a genetic deficiency of a guanine nucleotide-binding protein, termed Gs. The putative involvement of another G protein, contained in rods and cones, transducin, in the pathogenesis of the retinopathy is discussed.
This is a preview of subscription content, log in via an institution to check access.
References
Aguirre G, Farber D, Lolley R, Fletcher RT, Chader GJ (1978) Rod-cone dysplasia in Irish setters: a defect in cyclic GMP metabolism in visual cells. Science 201:1133–1134
Anderson HC (1983) Calcific diseases. A concept. Arch Pathol Lab Med 103:341–348
Avenet P, Hofmann F, Lindemann B (1988) Transduction in taste receptor cells requires cAMP-dependent protein kinase. Nature 331:351–354
Chase LR, Melson GL, Aurbach GD (1969) Pseudohypopara-thyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone. J Clin Invest 48:1832–1844
Farfel Z, Friedman E (1986) Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency. Ann Intern Med 105:197–199
Gouras P (1970) Electroretinography: some basic principles. Invest Ophthalmol 9:557–569
Graziano MP, Gilman AG (1987) Guanine nucleotide-binding regulatory proteins: mediators of transmembrane signaling. Trends Pharmacol Sci 8:478–481
Hammerstein W, Bischof G, Keck E (1982) A tapetoretinal degeneration with symmetrical calcifications of the basal ganglia. A hereditary disease. Eur Neurol 21:249–255
Illum F, Dupont E (1985) Prevalences of CT-detected calcification in the basial ganglia in idiopathic hypoparathyroidism. Neuroradiology 27:32–37
Levine MA, Downs RW, Moses AM, Breslau NA, Marx SJ, Lasker RD, Rizzoli RE, Aurbach GD, Spiegel AM (1983) Resistance to multiple hormones in patients with pseudohypoparathyroidism. Association with deficient activity of guanine nucleotide regulatory protein. Am J Med 74:545–556
Levine MA, Ahn TG, Klupt ST, Kaufman KD, Smallwood PM, Bourne HR, Sullivan KA, Van Dop C (1988) Genetic deficiency of the α subunit of the guanine nucleotide binding protein Gs as the molecular basis for Albright hereditary osteodystrophy: Proc Natl Acad Sci USA 85:617–621
Lolley RN, Farber DB, Rayborn ME, Hollyfield JG (1977) Cyclic GMP accumulation causes degeneration of photoreceptor cells: simulation of an inherited disease. Science 196:664–666
Nakamura T, Gold GH (1987) A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444
Spiegel AM, Levine MA, Aurbach GD, Downs RW, Marx SJ, Lasker RD, Moses AM, Breslau NA (1982) Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism. Am J Physiol 243:E37-E42
Spiegel AM, Gierschik P, Levine MA, Downs RW (1985) Clinical implications of guanine nucleotide-binding proteins as receptor-effector couplers. N Engl J Med 312:26–33
Weinstock RS, Wright HN, Spiegel AM, Levine MA, Moses AM (1986) Olfactory dysfunction in humans with deficient guanine nucleotide-binding protein. Nature 322:635–636
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ellie, E., Julien, J., Ferrer, X. et al. Extensive cerebral calcification and retinal changes in pseudohypoparathyroidism. J Neurol 236, 432–434 (1989). https://doi.org/10.1007/BF00314907
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00314907