24-year-old male patient with short stature, special educational needs and poor personal care.
Weight – 39kg, Height – 148cms (Normal: 157 – 167cms) with height-year corresponding to 12 - 13 years. Mental age – 6 years (IQ – 37).
Hypoplastic enamel leading to increased dental spacing
Trousseau and Chvostek signs were positive.
Radiograph of both feet revealed bilateral shortening of fourth metatarsal bones. There were also focal areas of soft tissue calcifications.
Radiograph of the hands revealed diffuse osteopenia with coarsening of trabecular bone and areas of soft tissue calcifications.
Computed Tomography of the brain showed extensive symmetrical calcification in bilateral lentiform nuclei, thalami, caudate nuclei, bilateral frontal, temporal and parietal subcortical regions and bilateral cerebellar hemispheres (dentate nuclei).
Laboratory investigations revealed hypocalcemia (S.Ca - 5.8mg/dl) , hyperphosphatemia (S. Phosphorus - 7.1mg/dl) and elevated parathyroid hormone level (S.PTH - 204.5pg/ml)
In view of the clinical, biochemical and imaging findings, a diagnosis of pseudohypoparathyroidism with PTH resistance was made.
Pseudohypoparathyroidism is an autosomal dominant familial metabolic disorder [1]. It is characterised by hypocalcaemia, hyperphosphataemia, raised serum levels of Parathyroid Hormone (PTH) and end organ resistance to the biological activity of PTH [2]. Fuller Albright first described this disease in 1942 [3]. The spectrum of typical physical features associated with it is termed Albright’s Hereditary Osteodystrophy [1].
The genetic basis of this disease is attributed to a molecular defect in the gene GNAS1 [1]. In addition to PTH, these patients may also show resistance to other hormones, namely Thyroid Stimulating Hormone (TSH), Growth Hormone (GH) and Gonadotropins [1]. The biochemical changes include decreased serum calcium with increased serum phosphorus and serum Parathyroid Hormone (PTH) levels with failure to respond to exogenously administered PTH [1, 4].
The characteristic phenotype includes short stature, obesity, brachymetaphalangia, soft tissue calcification, intracranial calcification and mild to moderate mental retardation [1, 2, 3, 4, 5]. Tetany, seizures or laryngeal stridor may occur secondary to hypocalcaemia [1]. Other features include cataracts, lenticular opacities and sensorineural hearing loss [1]. The oral manifestations of this disease include thin enamel, widened root canals and caries [5].
Imaging findings include brachydactyly, a very common finding which most often involves the fourth or fifth metacarpal/ metatarsal bones which may be associated with coning and premature fusion of the epiphysis [1]. Phalangeal shortening involving the distal phalanges may be seen [1]. Commonly, patients present with Potter's thumb, which is shortening of the distal phalanx of the thumb and is seen in this condition as an increased nail width-to-length ratio. Thickening of the calvarium with widening of diploic spaces and hyperostosis frontalis interna may be present [1]. In the axial skeleton there is loss of caudal widening of the lumbar interpedicular distance [1]. Ossification of the paravertebral ligaments may also be seen [1]. There may be associated bowing of the tibia and radius. Bony exostosis, slipped capital femoral epiphysis and coxa vara are also associated findings [1].
Computed Tomography of the brain usually reveals extensive bilateral symmetrical calcification involving the basal ganglia, thalamus, cerebellum, subcortical white matter and corona radiata which is a typical finding due to prolonged hypocalcaemia and hyperphosphatemia [1, 6].
A hyperparathyroid bone disease may be seen in some patients with pseudohypoparathyroidism due to variable responsiveness of the skeletal system to the elevated PTH levels [4]. Radiologically, it may be seen as generalised osteopenia, coarsened trabeculae and subperiosteal resorption [4].
Pseudohypoparathyroidism Type 1 A - Albright’s Hereditary Osteodystrophy
Based on the provided X-ray images of the hands and feet, the following findings are observed:
On cranial CT:
Regarding oral health, based on history and clinical examination, there is evidence of enamel hypoplasia and widened tooth spacing.
Combining the patient’s history (short stature, intellectual disability, dental abnormalities, positive signs of neuromuscular irritability due to hypocalcemia), as well as the imaging findings, possible diagnoses include:
Considering the patient’s age, clinical presentation (especially intellectual disability, short stature, enamel hypoplasia and widened dental spacing, positive Trousseau’s and Chvostek’s signs, lab findings of low calcium, high phosphate, and elevated PTH), as well as the typical imaging features (short finger/toe deformities, intracranial calcifications, etc.), the most likely diagnosis is:
Pseudohypoparathyroidism (Albright’s Hereditary Osteodystrophy).
Further confirmation can be obtained through genetic testing (screening for GNAS1 mutations) and a more comprehensive evaluation of other endocrine axes.
Given the patient’s skeletal deformities and the potential risk of muscle spasms, the exercise program must be gradual and individualized. The primary focus is on preserving and improving joint mobility, enhancing core and overall muscle strength, and avoiding excessive loads that may lead to musculoskeletal injury or hypocalcemic tetany.
Disclaimer: This report is a preliminary medical assessment and recommendation based on currently available information. It does not replace an in-person diagnosis or professional medical guidance. If you have any questions or experience significant changes in symptoms, please seek timely medical evaluation and further investigations or treatment.
Pseudohypoparathyroidism Type 1 A - Albright’s Hereditary Osteodystrophy
