Acrodysostosis

Overview

Acrodysostosis also known as Arkless-Graham syndrome or Maroteaux-Malamut syndrome is a rare congenital malformation syndrome which involves shortening of the knuckles of the legs and hands, mental deficiency in approximately 90% of affected children, and peculiar fecies. Other common abnormalities include short head (which is measured front to back i.e. brachycephaly), small broad upturned nose with flat nasal bridge, protruding jaw, Intrauterine growth retardation and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur. Most reported cases have been sporadic, but it has been suggested that the condition might be genetically related i.e. in a autosomal dominant mode of transmission. Both males and females are affected. The disorder has been associated with older parental age.

Differentiating Acrodysostosis From Other Diseases

Acrodysostosis be differentiated from other causes of abnormal parathyroid hormone(PTH) and parathyroid hormone resistance like Blomstrand chondrodysplasia, pseudohypoparathyroidism, hypomagnesemia, hypoparathyroidism and hyperparathyroidism.^[1]^[2]^[3]^[4]

Differential diagnosis of Pseudohypoparathyroidism
Disorders		Mechanism	Laboratory findings
Disorders		Mechanism	Serum PTH	Serum Calcium	Serum Phosphate	Other findings
Pseudohypoparathyroidism ^[1]^[2]^[3]	Type 1a	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH) Heterozygous GNAS inactivating mutations that reduce expression or function of Gα_s Genetic mutation disrupts both receptor-mediated activation of adenylyl cyclase and receptor-independent activation of the enzyme.	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 1b	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Familial– heterozygous deletions in STX16, NESP55, and/or AS exons or loss of methylation at GNAS	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 1c	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Heterozygous GNAS inactivating mutations that reduce expression or function of Gα_s Genetic mutation disrupts receptor-mediated activation of adenylyl cyclase but does not affect receptor-independent activation of the enzyme.	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 2	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH).	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D Normal urinary cAMP ↓ Urinary phosphate
	Pseudopseudohypoparathyroidism	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Combination of inactivating mutations of GNAS1 and Albright’s osteodystrophy	Normal	Normal	Normal	—
Hypoparathyroidism		There is deficiency of parathyroid hormone in hypoparathyroidism. Deficiency of parathyroid hormone causes body to decrease: Reabsorption of calcium from bone. Excretion of phosphate. Reabsorbtion of calcium from distal tubules. Vitamin D mediated absorption of calcium from intestine.	↓	↓	↑	↓ 1,25 Dihydroxy vitamin D Normal urinary cAMP Normal urinary phosphate
Hypomagnesemia^[5]^[4]		Decreased parathyroid hormone (PTH) secretion Skeletal resistance to parathyroid hormone (PTH)	Inappropriately ↓	Normal/↓	—	↓ serum magnesium ↓/Normal serum potassium
Acrodysostosis	Acrodysostosis type 1	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH) PRKAR1A germ-line mutation in the encoding gene resulting in parathyroid resistance	↑	↓	↑	Multiple hormone resistance
Acrodysostosis	Acrodysostosis type 2	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH) Phosphodiesterase 4D (PDE4D) gene mutation resulting in parathyroid resistance	↑	↓	↑	Multiple hormone resistance
Blomstrand chondrodysplasia		Genetic defectcausing end organ resistance to the action of parathyroid hormone (PTH) Homozygous or heterozygous mutations in both alleles encoding the type 1 parathyroid hormone receptor resulting in parathyroid resistance	↑	↓	↑	↓ Urinary Phosphate, ↑ Urinary cAMP
Hyperparathyroidism	Primary hyperparathyroidism	Increase in secretion of parathyroid hormone (PTH) from a primary process in parathyroid gland. Parathyroid hormone causes increase in serum calcium.	↑	↑	↓/Normal	Normal/↑ calcitriol
	Secondary hyperparathyroidism	Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium after long periods.	↑	↓/Normal	↑	—
	Tertiary hyperparathyroidism	Continuous elevation of parathyroid hormone(PTH) even after successful treatment of the secondary cause of elevated parathyroid hormone. Parathyroid hormone causes increase in serum calcium.	↑	↑	↑	—

References

Further Reading

↑ ^1.0 ^1.1 Levine MA (2012). “An update on the clinical and molecular characteristics of pseudohypoparathyroidism”. Curr Opin Endocrinol Diabetes Obes. 19 (6): 443–51. doi:10.1097/MED.0b013e32835a255c. PMC 3679535. PMID 23076042.
↑ ^2.0 ^2.1 Mantovani G (2011). “Clinical review: Pseudohypoparathyroidism: diagnosis and treatment”. J. Clin. Endocrinol. Metab. 96 (10): 3020–30. doi:10.1210/jc.2011-1048. PMID 21816789.
↑ ^3.0 ^3.1 Lee S, Mannstadt M, Guo J, Kim SM, Yi HS, Khatri A, Dean T, Okazaki M, Gardella TJ, Jüppner H (2015). “A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism”. J. Bone Miner. Res. 30 (10): 1803–13. doi:10.1002/jbmr.2532. PMC 4580526. PMID 25891861.
↑ ^4.0 ^4.1 Freitag JJ, Martin KJ, Conrades MB, Bellorin-Font E, Teitelbaum S, Klahr S, Slatopolsky E (1979). “Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone”. J. Clin. Invest. 64 (5): 1238–44. doi:10.1172/JCI109578. PMC 371269. PMID 227929.
↑ Jahnen-Dechent W, Ketteler M (2012). “Magnesium basics”. Clin Kidney J. 5 (Suppl 1): i3–i14. doi:10.1093/ndtplus/sfr163. PMC 4455825. PMID 26069819.

Template:WikiDoc Sources

[pmid23076042-1] 1.0 ^1.1 Levine MA (2012). “An update on the clinical and molecular characteristics of pseudohypoparathyroidism”. Curr Opin Endocrinol Diabetes Obes. 19 (6): 443–51. doi:10.1097/MED.0b013e32835a255c. PMC 3679535. PMID 23076042.

[pmid21816789-2] 2.0 ^2.1 Mantovani G (2011). “Clinical review: Pseudohypoparathyroidism: diagnosis and treatment”. J. Clin. Endocrinol. Metab. 96 (10): 3020–30. doi:10.1210/jc.2011-1048. PMID 21816789.

[pmid25891861-3] 3.0 ^3.1 Lee S, Mannstadt M, Guo J, Kim SM, Yi HS, Khatri A, Dean T, Okazaki M, Gardella TJ, Jüppner H (2015). “A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism”. J. Bone Miner. Res. 30 (10): 1803–13. doi:10.1002/jbmr.2532. PMC 4580526. PMID 25891861.

[pmid227929-4] 4.0 ^4.1 Freitag JJ, Martin KJ, Conrades MB, Bellorin-Font E, Teitelbaum S, Klahr S, Slatopolsky E (1979). “Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone”. J. Clin. Invest. 64 (5): 1238–44. doi:10.1172/JCI109578. PMC 371269. PMID 227929.

[pmid26069819-5] Jahnen-Dechent W, Ketteler M (2012). “Magnesium basics”. Clin Kidney J. 5 (Suppl 1): i3–i14. doi:10.1093/ndtplus/sfr163. PMC 4455825. PMID 26069819.

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Acrodysostosis

Overview

Differentiating Acrodysostosis From Other Diseases

References

Further Reading

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