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Pseudopseudohypoparathyroidism
Clinical Picture
Pseudopseudohypoparathyroidism Ronald C W Ma, Clive S Cockram Lancet 2009; 374: 2090 Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong (R C W Ma MRCP, Prof C S Cockram FRCP) Correspondence to: Dr Ronald C W Ma, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong [email protected]
A 15-year-old girl presented with short stature; her height was 1·42 m (3 cm below third percentile) and her bodyweight was 41·8 kg (around 50th percentile). She had a round face and several subcutaneous nodules over her forehead, hands, and knees. She had hypoplasia of her fourth and fifth metacarpals bilaterally (figure). Serum calcium and parathormone concentrations were normal. Genetic testing showed that she was heterozygous for a non-sense mutation affecting GNAS, confirming the diagnosis of pseudopseudohypoparathyroidism. GNAS
encodes the α-chain of the heterotrimeric G-protein Gs, which couples receptors for many hormones and neurotransmitters to activation of adenylyl cyclase. Pseudopseudohypoparathyroidism is indicative of genomic imprinting. Patients who inherit the mutation from the paternal allele develop pseudopseudohypoparathyroidism, whereas inheritance from the maternal allele leads to pseudopseudohypoparathyroidism and renal resistance to parathormone and hypocalcaemia. Brachydactyly is due to premature closure of the epiphyses in the metacarpals.
R
Figure: Brachydactyly in a patient with pseudopseudohypoparathyroidism
2090
www.thelancet.com Vol 374 December 19/26, 2009
Pseudopseudohypoparathyroidism Ronald C W Ma, Clive S Cockram Lancet 2009; 374: 2090 Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong (R C W Ma MRCP, Prof C S Cockram FRCP) Correspondence to: Dr Ronald C W Ma, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong [email protected]
A 15-year-old girl presented with short stature; her height was 1·42 m (3 cm below third percentile) and her bodyweight was 41·8 kg (around 50th percentile). She had a round face and several subcutaneous nodules over her forehead, hands, and knees. She had hypoplasia of her fourth and fifth metacarpals bilaterally (figure). Serum calcium and parathormone concentrations were normal. Genetic testing showed that she was heterozygous for a non-sense mutation affecting GNAS, confirming the diagnosis of pseudopseudohypoparathyroidism. GNAS
encodes the α-chain of the heterotrimeric G-protein Gs, which couples receptors for many hormones and neurotransmitters to activation of adenylyl cyclase. Pseudopseudohypoparathyroidism is indicative of genomic imprinting. Patients who inherit the mutation from the paternal allele develop pseudopseudohypoparathyroidism, whereas inheritance from the maternal allele leads to pseudopseudohypoparathyroidism and renal resistance to parathormone and hypocalcaemia. Brachydactyly is due to premature closure of the epiphyses in the metacarpals.
R
Figure: Brachydactyly in a patient with pseudopseudohypoparathyroidism
2090
www.thelancet.com Vol 374 December 19/26, 2009