J Korean Endocr Soc.  2009 Jun;24(2):138-143. 10.3803/jkes.2009.24.2.138.

A Case of Pseudopseudohypoparathyroidism with Normal Stature

• Kim SR
• Doh YJ
• Kim HK
• Moon SS
• Lee JY
• Jeon JH
• Kim SW
• Kim BW
• Lee IK
• Kim JG

• KMID: 1468510
• DOI: http://doi.org/10.3803/jkes.2009.24.2.138

Abstract

Pseudopseudohypoparathyroidism (PPHP) is characterized by the phenotype of Albright hereditary osteodystrophy (AHO) alone without biochemical evidence of multihormone resistance, which is unlike pseudohypoparathyroidism. AHO is associated with characteristic developmental abnormalities that include a short stocky stature, a short neck, brachydactyly, a round face, central obesity, mental retardation and subcutaneous ossifications. AHO is an autosomal dominant disease that's caused by heterozygous inactivating mutations in the Gsalpha gene (GNAS1). Melanocortin-4 receptor (MC4R) is a hypothalamic Gs-coupled receptor that is thought to mediate the central effect of leptin on satiety. MC4R mutations cause morbid obesity starting in infancy, as well as an elevated leptin level. A 62 year old man with a height of 171.5 cm, a round face, a short neck, central obesity and brachydactyly had normal ranges of serum calcium, phosphorus and PTH and a normal Ellsworth-Howard test. GNAS1 gene analysis revealed substitution of alanine to cysteine in the 165 codon of exon 6 and substitution of alanine to cysteine in the 231 codon of exon 9. Two known SNPs (Cyt-1042Thy, Gua-719Ade) in the MC4R were detected in the patient. We report here on a case of PPHP and the patient had normal stature. We propose that MC4R may have contributed to the obesity & normal stature of this patient.

Keyword

Albright hereditary osteodystrophy; GNAS1; MC4R; normal stature; pseudopseudohypoparathyroidism

MeSH Terms

Alanine
Alkenes
Brachydactyly
Calcium
Codon
Cysteine
Exons
Fibrous Dysplasia, Polyostotic
Humans
Intellectual Disability
Leptin
Neck
Obesity
Obesity, Abdominal
Obesity, Morbid
Phenotype
Phosphorus
Polymorphism, Single Nucleotide
Pseudohypoparathyroidism
Pseudopseudohypoparathyroidism
Receptor, Melanocortin, Type 4
Reference Values
Alanine
Alkenes
Calcium
Codon
Cysteine
Fibrous Dysplasia, Polyostotic
Leptin
Phosphorus
Receptor, Melanocortin, Type 4

Figure

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  Fig. 1 Normal stature, obesity, round face, short neck (A), short appearing third and fourth fingers of Rt. hand and second, third and fourth fingers of Lt. hand, flat third and fourth knuckles of Rt. hand and second, third and fourth knuckles of Lt. hand (B), shortened first and fourth toes of Rt. foot and first toes of Lt. foot (C).

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  Fig. 2 Plain radiograph of hand with shortened of Rt. third, fourth metacarpals and second, third and fourth metacarpals (A), foot with shortened of Rt. first, fourth metatarsals and Lt. first metatarasal (B).

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  Fig. 3 Results of Ellsworth-Howard test. Urine cAMP, phosphate excretion of before and after PTH injection (U-P : (U3 + U4) - (U1 + U2) = 88.8 mg/dL, U-cAMP : U3 - U2 = 140.7 mcmol/l). U1, urine 2 hours before PTH injection; U2, urine 1 hour before PTH injection; U3, urine 1 hour after PTH injection; U4, urine 2 hours after PTH injection.

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  Fig. 4 Electrophoresis of PCR products in Arg165Cys and Arg231Cys polymorphism analysis of GNAS1 gene by ARMS. A: Arg165Cys polymorphism product. B. Arg231Cys polymorphism product. W, Wild type; S, SNP type; W/W, Wild type homozygote; S/S, SNP homozygote; W/S, heterozygote; M, 100bp ladder.

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