1 - Pediatrics Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central
2 - Endocrinology Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central
- Congresso internacional
- Apresentado sob forma de poster
Resumo:
Background: Pseudohypoparathyroidism (PHP) and related disorders are a rare group characterized by end-organ resistance to the action of parathyroid hormone (PTH). Albright’s hereditary osteodystrophy (AHO), also known as Pseudohypoparathyroidism type 1 A (PHP1A), was the first subtype described. It is characterized by hypocalcemia and hyperphosphatemia despite elevated PTH, along with an unusual constellation of physical findings. The mainstay of the diagnosis is its clinical and biochemical characteristics. Identifying the molecular cause confirms the clinical diagnosis and allows characterization of the subtypes of the disease.
Case Presentation: We describe the clinical case of a 6-year-old female patient who presented to the emergency department with a two weeks course of diplopia and associated headache. A peculiar face and a stocky built was noted, but she had a normal neurological and ophthalmological physical examination. A head CT scan was performed and showed bilateral calcifications in both basal ganglia and white subcortical substance. Laboratory investigation revealed serum hypocalcemia of 4,9 mg/dl, hyperphosphatemia and an elevated serum PTH level of 816,30pg/ ml, with subclinical hypothyroidism (elevated TSH and diminished fT4). Electrocardiogram (EKG) detected a prolonged QTc interval of 524ms. Reviewing the physical examination with attention to dysmorphic characteristics, brachydactily, with shortening of metacarpal and 4th and 5th metatarsal bones bilaterally, was also noted. She was admitted and initially treated with intravenous calcium and oral vitamin D analog. A progressive normalization of the phosphocalcium metabolism and the EKG was verified as well as resolution of the clinical symptoms. A skeletal radiological study was conducted and showed decreased bone mineral density and higher than expected bone age, but no ectopic ossifications. Findings were consistent with Pseudohypoparathyroidism with Albright’s hereditary osteodystrophy (AHO) phenotype and genetic analysis confirmed the diagnosis with identification of pathogenic variant in heterozygosity in the GNAS gene.
Discussion: Early diagnosis can be challenging due to symptom heterogeneity and overlap of clinical findings, as exemplified in the clinical case we describe. The neurological findings set the clue for this endocrinological disorder. The level of suspicion was of determinant importance, allowing specific interventions that are crucial for the efficiency of treatment and can be lifesaving. Therapeutic management consists mostly of normalization of calcium levels, and follow-up requires a multidisciplinary team to manage and follow other clinical aspects and potential complications.