Year : 2009 | Volume
: 27 | Issue : 3 | Page : 184--188
Albright hereditary osteodystrophy: A rare case report
M Goswami, M Verma, A Singh, H Grewal, G Kumar
Department of Pediatric and Preventive Dentistry, Maulana Azad Institute of Dental Sciences, New Delhi 110 002, India
Department of Pediatric and Preventive Dentistry, Maulana Azad Institute of Dental Sciences, New Delhi 110 002
Albright hereditary osteodystrophy (AHO) is a rare hereditary metabolic disorder that may be associated with or without resistant to parathyroid hormone (pseudohypoparathyroidism). It is commonly characterized by a constellation of physical features of short stature, round face, short neck, and small metacarpals and metatarsals, mild mental retardation, osteoporosis, subcutaneous calcification, and sometimes olfactory and hearing functional defect. Hypocalcaemia and hyperphosphatemia are the most important manifestations of the case. We report a clinical case of siblings with AHO with reduced Gs-alpha activity and we discuss their clinical features with oral manifestations, radiographic findings, laboratory tests along with treatment.
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Goswami M, Verma M, Singh A, Grewal H, Kumar G. Albright hereditary osteodystrophy: A rare case report.J Indian Soc Pedod Prev Dent 2009;27:184-188
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Goswami M, Verma M, Singh A, Grewal H, Kumar G. Albright hereditary osteodystrophy: A rare case report. J Indian Soc Pedod Prev Dent [serial online] 2009 [cited 2022 Jul 2 ];27:184-188
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Albright hereditary osteodystrophy (AHO) is characterized by a metabolic disorder that can be inherited in an autosomal dominant, autosomal recessive, or X-linked dominant form. It was first described by "Fuller Albright" in 1942. It is also known as pseudohypoparathyrodism (PHP) and acrodyostosis.  It is a heterogeneous group of disorder characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone, and insensitivity to the biological activity of PTH due to resistance toward parathyroid hormone. This defect is caused by gene mutation in GNAS1 gene, which results in partial or total deficiency of Gs-alpha activity and thus involves the impairing of function of the biochemical pathways responsible for the activation of parathormone receptors; therefore it leads to resistance to PTH action. Classification of PPH has been presented in [Table 1].
Apart from features that are common to all forms of hypoparathyroidism, i.e., short stature which is usually evident in late childhood), obesity, mental retardation, subcutaneous ossification, brachydactyly (metacarpal and metatarsal shortening), hypogonadism, and hypothyroidism.  Dental defects include enamel hypoplasia and blunt root development .It is an important cause of delayed eruption of teeth.  There is considerable phenotypic variability of the disease in the same family and in the same generation. Hence, a high index of suspicion should be kept while investigating delayed teeth eruption with teeth hypoplasia, along with short stature and hypocalcemia, so that an extended family examination can offer an important clue to decide the treatment to control signs and symptoms of hypocalcemia by administrating calcium and Vitamin D along with periodic monitoring of calcium serum levels and urinary excretion.
A 13-year-old girl reported to the Department of Pediatric Dentistry with the chief complaint of non-eruption of some teeth along with the yellowish-white marks/stains on teeth. Following the patient history, it was revealed that she was born to nonconsanguineous parents who have total three children: one elder male child, second female child (our patient), and third male child. We examined the whole family [Table 2] and found that the patient had delayed milestones, which were also seen in her elder brother but the younger sibling was in good health. General body examination revealed that both the patient and her brother have short stature, round chubby faces with short neck, frontal bossing, depressed nasal bridge, blue sclera, bowing of legs, short stubby fingers, low mental caliber, and delayed puberty [Figure 1]. On oroclinical examination, it was found that both had delayed dental age and has multiple carious teeth. Whole dentition shows hypoplastic occlusion surface with angle class II malocclusion with anterior open bite [Figure 2]. The mother had normal stature and body habitus but short of left ring finger and both fourth toes [Figure 3]. Series of investigations were done for both the affected siblings, i.e., radiographic examination (hand-wrist x-rays, x-rays of the feet, x-ray of the skull, OPG), laboratory investigations (serum calcium, serum phosphate, TSH, PTH), and genetic evaluation (Gs-alpha activity).
Radiographic examination revealed delayed bone age, osteopenia, and short metatarsal and metacarpal (mainly 2, 3, and 4). Soft tissue calcification was observed in right wrist and right feet (brother) [Figure 4] and in right hand (patient) [Figure 5]. Silver beaten appearance of skull is seen in her brother [Figure 6]. On radiograph of the hand, a line is drawn transgential to the distal portion of the fourth and fifth metacarpals. In normal subjects, it should not intersect the third metacarpal [Figure 7],[Figure 8],[Figure 9],[Figure 10]. This sign is positive in our patients (Archibalds sign). 
Laboratory investigations revealed hypocalcaemia (serum calcium 4.2 mg/dl), hyperphosphatemia (serum phosphate 4-6.7 mg/dl), decreased serum T4, and elevated TSH (12 mIU/ml). Various such levels are shown in [Table 3].
Genetic evaluation revealed that Gs-alpha activity in the erythrocyte membrane was decreased in both siblings and mother.
The biochemical profile along with characteristic phenotype of both the siblings supports the diagnosis of PPH type Ia, i.e., AHO, while the mother expressed only AHO phenotype; otherwise she is normocalcemic and has no other sign of hormone resistance apart from reduced Gs-alpha activity. These findings support the diagnosis of pseudopseudohypoparathyrodism (PPHP). For the management, both siblings were initiated on thyroxin and calcitriol along with calcium supplements, and patient underwent various restorations and root canal treatment of multiple carious teeth and they were motivated to practice good oral hygiene. After 6 months, a significant improvement was observed, and the patients decided to go for orthoganthous and orthodontic treatment for esthetics and functional correction of malocclusion.
PHP is a term applied to a heterogeneous group of disorders where the most common feature is the resistance to parathyroid hormone.  Most of the patients have hypocalcemia and hyperphosphatemia despite elevated concentration of parathyroid hormone in plasma. This is due to the loss of the phosphaturic action of parathyroid hormone and reduced formation of 1, 25-dihydroxy vitamin-D with resultant defective mobilization of calcium from bone and reduced GIT absorption of calcium. PHP type Ia is associated with resistance to multiple hormones in addition to parathyroid hormone and with a constellation of physical abnormalities collectively termed as AHO.  The typical phenotypic features consist of round face with short and stocky built. There is brachydactyly with dimpling of the dorsum of hand instead of knuckles when fist is clinched. The most commonly affected are short 4th and 5th metacarpals and metatarsals. These defects are usually bilateral.  And this may be due to premature skeletal development and closure of epiphysis. Our case also coincides with these findings with shortened metatarsals in both siblings. Obesity and mild mental retardation are often seen in these patients because lipolytic factors act by stimulating cAMP formation, and abnormalities in cAMP metabolism are associated with learning defect. Thickened calvaria, and shortening and broadening of distal phalanges with subcutaneous calcification are observed. In our case, we noticed a typical silver beaten appearance of skull in one of the siblings, which coincides with these findings. Primary hypothyroidism and reproductive dysfunction commonly occur in these patients. Women may have delayed puberty, oligomenorrhea, and infertility.  The oral manifestations found in literature include enamel aplasia/hypoplasia, late teeth eruption, and enlarged radicular channels susceptible to carries-such manifestations are observed in our study.  In addition, there was also the presence of malocclusion impairing proper oral hygiene and favoring the accumulation of bacterial plaque and calculus. Patients with PHP Ia have AHO phenotype resistance to G-protein-coupled hormone, attenuated response to urinary phosphate and cAMP excretion after intravenous infusion of synthetic PTH, and decreased Gs-alpha activity.  In some patients, this phenotype is found without biochemical evidence of PTH resistance. This has been termed as PPHP.  The abnormalities in various types of PHP have been depicted in the [Table 1].
A variety of disorders shares certain features in common with PHP type Ia, but in general is readily distinguished from it. Therefore differential diagnosis has to be made before deciding for appropriate diagnosis. Soft tissue ossification is present in myositis ossificans but differ in location (muscle) from that in PHP Ia (subcutaneous). The pattern of metacarpal shortening differs in PHP Ia and Turner syndrome, but the latter is not associated with resistance to PTH. The main difference now remains secondary hyperparathyroidism. Alkaline phosphtase levels are usually increased manifolds in this condition with characteristic appearance of ostitis fibrosa cystica.
All patients with severe symptomatic hypocalcemia should be treated with intravenous calcium. Administration of oral calcium and alpha hydroxylated vitamin-D metabolite such as cholecalciferol remains the mainstay of treatment and with close observation periodically. The dental treatment involves the management of carious teeth along with planning for correction of malocclusion.
The findings of general andoral manifestation of AHO described in our report contribute to the clinical picture of AHO that is developing in the literature. Various changes in patient with AHO continue to be the object of many studies, since there is little information on the oral manifestation of this disease, which hinders a better understanding of possible correlation between metabolic dysfunction and oral manifestation. The finding of this study could also facilitate the development of multidisciplinary approach among medical and dental professionals to promote precise diagnosis since there is considerable phenotypic variability of the disease in the same family and same generation. This more precise diagnosis and knowledge of AHO behavior could facilitate better planning of dental treatment of these patients with positive effect on their general health.
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