Ans: Pseudohypoparathyroidism - type 1a aka Albright's hereditary osteodystrophy Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Patients have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is actually appropriately high (due to the hypocalcemia). Its pathogenesis has been linked to dysfunctional G Proteins (in particular, Gs alpha subunit). pseudohypoparathyroidism comes in 3 flavors : type 1a, 1b and 2 The typical physical features in the image above is characteristic of type 1a, called - Albright's hereditary osteodystrophy Individuals with Albright’s hereditary osteodystrophy have short stature, characteristically shortened fourth and fifth metacarpals, rounded facies, and often mild mental retardation. Credit to Dr Angela for solving this tough challenge. P.S : add 1 more pseudo and u get the longest word in the english dictionary - pseudopseudohypoparathyroidism !!! Pseudopseudohypoparathyroidism (pseudoPHP) is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal. (-:
Related Self Assessment Question [FONT="]A 4-year-old child has mental retardation, shortness of stature, brachydactyly (especially of the fourth and fifth digits), and obesity with round facies and short neck. The child is followed by an ophthalmologist for subcapsular cataracts, and has previously been noted to have cutaneous and subcutaneous calcifications, as well as perivascular calcifications of the basal ganglia. This patient is most likely to have which of the following features?[/FONT] [FONT="]A. Hypercalcemia[/FONT] [FONT="]B. Hypophosphatemia[/FONT] [FONT="]C. Elevated concentrations of parathyroid hormone[/FONT] [FONT="]D. Advanced height age[/FONT] [FONT="]E. Decreased bone density, particularly in the skull[/FONT] [FONT="] [/FONT] [FONT="]EXPLANATION: [/FONT] [FONT="]The patient with the features listed likely has pseudohypoparathyroidism (Albright hereditary osteodystrophy). Such patients have chemical findings of hypoparathyroidism (low calcium, high phosphorus), but parathyroid hormone levels are high, indicating resistance to the action of this hormone. Parathyroid hormone infusion does not produce a phosphaturic response. Phenotypically, these patients demonstrate shortness of stature with delayed bone age, mental retardation, increased bone density throughout the body (especially evident in the skull), brachydactyly (especially of the fourth and fifth digits), obesity with round facies and short neck, subcapsular cataracts, cutaneous and subcutaneous calcifications, and perivascular calcifications of the basal ganglia. [/FONT] [FONT="]The answer is C.[/FONT]
Another Self Assessment Question on the topic [FONT=&]A short, 4-year-old, mentally retarded child has brachydactyly of the fourth and fifth digits; obesity with round facies; short neck; subcapsular cataracts; and cutaneous, subcutaneous, and perivascular calcifications of the basal ganglia. For this disorder, select the serum concentration of calcium (Ca2+) and phosphate (PO4) with which it is most likely to be associated.[/FONT] [FONT=&] A. Low PO4, normal Ca[/FONT] [FONT=&]B. Low PO4, high Ca[/FONT] [FONT=&]C. Normal PO4, low Ca[/FONT] [FONT=&]D. Normal PO4, normal Ca[/FONT] [FONT=&]E. High PO4, low Ca[/FONT] [FONT=&]EXPLANATION: [/FONT] [FONT=&] This patient has a form of pseudohypoparathyroidism (Albright hereditary osteodystrophy). Patients with pseudohypoparathyroidism have the same chemical abnormality (low Ca, high PO4) as those with hypoparathyroidism. They are distinguished from the latter group by the phenotypic features demonstrated by the girl in the question (Albright hereditary osteodystrophy) and high serum concentration of parathyroid hormone. The basic abnormality in these patients is the unresponsiveness of the renal tubules to parathyroid hormone. They are classified into two groups, depending on the site of the defect. Type I patients have failure to generate cyclic adenosine monophosphate (AMP) and do not have an increase in urinary concentration of cyclic AMP or phosphate in response to parathyroid hormone. Type II patients have a defect in the renal tubules that causes failure to respond to high concentrations of cyclic AMP. These patients, if given parathyroid hormone, have increased urinary excretion of cyclic AMP but not of phosphate.[/FONT] [FONT=&]The answer is E.[/FONT] A 5-day-old girl has brachydactyly, round facies, and short neck. All the syndromes listed below are associated with overweight conditions in children. For the other clinical findings in this patient, select the syndrome with which it is most likely to be associated. A. Prader-Willi syndrome B. Laurence-Moon-Biedl syndrome C. Cushing syndrome D. Fröhlich syndrome E. Pseudohypoparathyroidism F. Polycystic ovary syndrome G. Type 2 diabetes EXPLANATION: Patients with type 2 diabetes mellitus have insulin resistance in their skeletal muscles, increased hepatic glucose production, and decreased insulin secretion in response to elevated levels of glucose. They also develop hyperlipidemia and many complications of chronic hyperglycemia. Acanthosis nigricans, as described in the question, is a common finding in type 2 diabetes. The Prader-Willi syndrome is a disorder consisting of hypotonia, hypogonadism, hyperphagia after the newborn period, hypomentia, and obesity. A deletion of a portion of chromosome 15 has been found in approximately 70% of patients. Children affected by this syndrome exhibit little movement in utero and are hypotonic during the neonatal period. Feeding difficulties and failure to thrive can be the presenting complaints in the first year; later, obesity becomes the most common presenting complaint. The enormous food intake of affected children is thought to be caused by a defect in the satiety center in the hypothalamus. Stringent caloric restriction is the only known treatment. Laurence-Moon-Biedl (Bardet-Biedl) syndrome is transmitted as an autosomal recessive trait. Obesity, mental retardation, hypogonadism, polydactyly, and retinitis pigmentosa with night blindness are the principal findings in affected children. There is no known effective treatment. Fröhlich syndrome, also known as adiposogenital dystrophy, is a rare cause of childhood obesity associated with a hypothalamic tumor. Pseudohypoparathyroidism is a collective term for a variety of diseases. Affected patients have biochemical findings (low serum calcium and high serum phosphorus levels) similar to those associated with hypoparathyroidism, but they also have high levels of endogenous parathyroid hormone; in addition, exogenous parathyroid hormone fails to increase their phosphate excretion or raise their serum calcium level. The defects in these patients appear to be at the hormone receptor site or in the adenylate cyclase-cyclic AMP system. The symptoms of pseudohypoparathyroidism are caused by hypocalcemia. Affected children are short, round-faced, and mildly retarded. Metacarpals and metatarsals are shortened, and subcutaneous and basal ganglia calcifications as well as cataracts can be present. The current treatment consists of large doses of vitamin D and reduction of the phosphate load. Polycystic ovary disease classically presents at or shortly after puberty with obesity, hirsutism, and secondary amenorrhea. Later, these women have anovulatory infertility. The cause of this condition is not entirely clear. The initial complaint in Cushing syndrome may be obesity. Accumulation of fat in the face, neck, and trunk causes the characteristic "buffalo hump" and "moon" facies. Characteristic features include growth failure, muscle wasting, thinning of the skin, plethora, and hypertension. The bone age of affected patients is retarded, and osteoporosis can be present. The disorder results from an excess of glucocorticoids that may be caused by a primary adrenal abnormality (adenoma or carcinoma) or secondary hypercortisolism, which may be owing to excess adrenocorticotropin. Exogenous glucocorticoids administered in supraphysiologic doses for a prolonged period of time will produce a similar picture in normal subjects. The answer is E.
