Pseudohypoparathyroidism: Challenges in Early Recognition and Diagnosis of a Rare Hereditary Disorder

TL;DR

This paper discusses the challenges in diagnosing pseudohypoparathyroidism, a rare genetic disorder, and highlights the importance of genetic testing for early and accurate identification.

Contribution

The paper presents a case where genetic testing led to the correct diagnosis of PHP1A in an infant initially misdiagnosed with congenital hypothyroidism.

Findings

A maternally inherited GNAS variant was identified through whole exome sequencing in a patient with syndromic features.

PHP1A was confirmed at age five with biochemical evidence of hypocalcemia, hyperphosphatemia, and elevated PTH.

Early genetic testing and multidisciplinary care are crucial for accurate diagnosis and improved outcomes in PHP.

Abstract

Pseudohypoparathyroidism (PHP) is an uncommon endocrine condition marked by an impaired response to parathyroid hormone (PTH), which results in biochemical abnormalities. Clinical manifestations can vary significantly, occasionally resembling other endocrine disorders. Genetic testing plays a critical role in distinguishing PHP from other conditions, as it enables precise diagnosis even when classical features are not initially present.

We report the case of a male infant initially diagnosed with congenital hypothyroidism (CH) through neonatal screening and treated with levothyroxine. While growing up, the patient developed syndromic features, including facial dysmorphisms, global developmental delay, behavioural issues, and early-onset obesity. Whole exome sequencing (WES), prompted by the complex phenotype, identified a maternally inherited GNAS variant. This led to the suspicion of PHP1A, which was subsequently confirmed at five years of age when laboratory reevaluation revealed hypocalcemia, hyperphosphatemia, and elevated PTH levels. PHP can mimic isolated CH in early presentations, often delaying recognition.

This case underscores the pivotal role of genetic testing in diagnosing PHP. Early genetic evaluation and multidisciplinary care are essential for accurate diagnosis, tailored treatment, and long-term monitoring, ultimately improving patient outcomes.

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