Albright’s Hereditary Osteodystrophy: a Rare Cause of Hip Avascular Necrosis: a Case Report

Case Presentation

J Pediatri Endocrinol. 2019; 4(1): 1026.

Albright’s Hereditary Osteodystrophy: a Rare Cause of Hip Avascular Necrosis: a Case Report

Salman A*

Department of Pediatric Endocrinology, Qassim University, Saudi Arabia

*Corresponding author: Almansour Salman, Department of Pediatric Endocrinology, Qassim University, Qassim, Saudi Arabia

Received: November 20, 2018; Accepted: January 28, 2019; Published: February 04, 2019

Abstract

Pseudohypoparathyroidism (PHP) is a rare genetic disease that is characterized by a clinical picture of hypoparathyroidism, but with a high level of Parathyroid Hormone (PTH) due to its resistance. Albright’s Hereditary Osteodystrophy (AHO) is a type of PHP that it has distinctive features such as obesity, short stature, brachydactyly and subcutaneous calcification. A wide variety of clinical and biochemical presentations have been reported in the past. We review here a case of AHO with rare presentation in pediatric populations. A four and half year old girl with a documented history of learning disability and attention deficit presented to the orthopedic clinic with the complaint of pain in the right hip, which was diagnosed as avascular necrosis of hip. During routine workup, she was found to have a low vitamin D level with high Thyroid Stimulating Hormone (TSH) and Parathyroid Hormone (PTH). She was managed initially as a case of Vitamin d dependent rickets with secondary hyperparathyroidism. The child was of comparatively short stature for her age, overweight, with a round face typical of AHO, dental caries and with short and broadened hands and feet. Her lab results showed normal calcium at 2.32 mmol/L, normal phosphate 1.78 mmol/L, high PTH 225 ng/L, high TSH 14.5 mU/L, normal Free-triiodothyroxine 17.8 P mol/L, and low Vitamin D3 (cholecalciferol) 40 nmol/L. An imaging study of her hand revealed short broad metacarpal and pharyngeal bones with low bone mass. Based on those clinical and lab findings, PHP was expected. The gene sequencing study of GNAS1 gene was sent and came positive for heterozygous mutation and confirmed the diagnosis of Albright’s Hereditary Osteodystrophy (AHO).

Keywords: Albright’s hereditary osteodystrophy; Hypoparathyroidism; Pseudohypoparathyroidism

Hereditary Osteodystrophy a Rare Cause of Hip Avascular Necrosis

Pseudohypoparathyroidism is a rare disease that was discovered initially by Fuller Albright and his colleagues in 1942 when they found group a of patients who presented with pictures of hypoparathyroidism (hypocalcemia, hyperphosphatemia) but their calcium and phosphate level failed to show responses after repeated injections of bovine parathyroid extract. It was concluded that the mechanism was end organ resistance that primarily impairs the renal actions of PTH, rather than deficiency in the hormones [1,2]. PHP was divided into type 1 and type 2, and type 1 subdivided to 1a, 1b, 1c, with the most common form being type 1a [3]. Presence of some distinctive features (short stature, rounded face, obesity, cutaneous ossification and metacarpophalangeal abnormalities) along with parathyroid hormone resistance indicate that which is known as Albright’s Hereditary Osteodystrophy (AHO) [4] [4].

PHP-1a is caused by heterozygous loss-of-function mutations in the Gs-alpha isoform of the GNAS gene on the maternal allele, which results in expression of the protein only from the paternal allele. Pseudopseudo hypoparathyroidism (PPHP) is a similar disorder characterized by features of AHO but with normal biochemistry and is caused by “mutations resulting in loss of function of the Gsalpha isoform of the GNAS gene on the paternal allele and resultant expression of the protein only from the maternal allele” [3,5,6]. Patients with type 1b have Renal PTH resistant hypocalcaemia and hyperphosphatemia, and imprinting/methylation defects at the GNAS locus, but they lack the features of AHO [7].

Many patients have been described with normocalcemia, with resistance to PTH [5]. Patients with PHP1a can present with hormonal resistance other than PTH such as TSH, Growth Hormone-Releasing Hormone (GHRH), gonadotropins and calcitonin. Hypothyroidism secondary to TSH resistance is common and has been the presenting feature in some neonates, and the explanation behind this is that the Thyroid-Stimulating Hormone (TSH) receptor is also coupled to adenylyl cyclase by Gs proteins, which is coded by the GNAS protein [1,3,6,8,9,10].

Case Presentation

Herein we report a case of pseudohypoparathyroidism type-1a in a child who presented with avascular necrosis of the hip. This etiology is not one that is typical or well documented, and that highlights the importance of this as a rare presentation.

A four and half year old girl presented to the orthopedic clinic in a local hospital with the complaint of pain in her right hip for the last year prior to presentation. The x-ray showed deformity and fragmentation of the right hip joint. The patient was referred to our hospital and her condition was diagnosed by our orthopedic surgeon as avascular necrosis of right hip. This child had been born preterm at 34 weeks, and was delivered by caesarian section with no problems in the neonatal period. She was referred to the endocrine clinic initially at age of 5 years because of Cushioned features. She has a history of learning disability and attention deficit, a medication history of using prednisolone only for several days (unknown dosage and duration), and a documented history of gaining weight and constipation.

There was no history of abnormal movement, with no vomiting, diarrhea, fractures or decrease in activity. She was on a regular diet with only occasional sun exposure, and her parents were consanguineous with no similar family history of complaints. Initially she was treated as a case of vitamin D-dependent rickets with secondary hyperparathyroidism (after showing low vitamin D level with normal ACTH and cortisol) and she was started on calcium Sandoz 500 mg once daily and cholecalciferol 6 drops daily.

Her vital signs were: heart rate 62 beats per minute, blood pressure 116/69 with normal temperature and oxygen saturation. Patient’s height was 96 cm (at-1.69 SDS), her weight was 20.2 kg (on 90th percentile), and her appearance was overweight with rounded face, dental caries, no striae, and no bone deformities. This patient was able to walk freely without limping, and there was no noted alopecia. The patient has short, broad hands and feet that will become more obvious later on life (Figure 1,2) with leg length discrepancy. Her lab results showed calcium 2.32 mmol/L (2.10-2.60), phosphate 1.78 mmol/L (1.20-1.95), PTH 225 ng/L (15-65), TSH 14.5 mU/L (0,27-4.20), Free triiodothyroxine 17.8 Pmol/L (12-22), alkaline phosphatase 290 U/L (100-240), Vitamin D3 (cholecalciferol) 40 nmol/L (61-200). The imaging-study of the patient’s hand revealed short broad metacarpal and pharyngeal bones with low bone mass (Figure 3).