Case Reports
Molecular Diagnosis and Clinical Characterization of Pseudohypoparathyroidism Type-Ib in a Patient With Mild Albright’s Hereditary Osteodystrophy-Like Features, Epileptic Seizures, and Defective Renal Handling of Uric Acid

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ABSTRACT

We describe a patient who presented with epileptic seizures unresponsive to anticonvulsive treatment. Laboratory investigations demonstrated epileptiform seizure activity in the brain but also revealed severe hypocalcemia, hyperphosphatemia, and elevated serum parathyroid hormone. In addition, the patient showed a reduced serum level of 25-[OH]-vitamin D. The diagnosis of pseudohypoparathyroidism type-Ib (PHP-Ib) was made based on these clinical findings and upon identification of a 3-kb deletion within the STX16 locus, a genetic defect frequently associated with autosomal dominant PHP-Ib. This mutation was also present in the patient’s unaffected mother and her affected sister. Despite the molecular diagnosis of PHP-Ib, which is characterized by parathyroid hormone resistance in the absence of Albright’s hereditary osteodystrophy (AHO), the patient had a round face, slightly short stature, and short fourth metacarpals, which were consistent with mild AHO. The patient and her affected sister, who lacked AHO-like features, showed reduced serum levels of uric acid and increased fractional excretion of uric acid, a finding that was reported only once previously for PHP-Ib. Unlike the previous report, the fractional uric acid excretion and serum uric acid levels returned to normal in our patient and her sister after 3 months of treatment period. These findings underscore several important points with respect to the pathogenesis and clinical presentation of PHP-Ib. Furthermore, the findings in the index case present interesting novel aspects, including a previously undescribed coexistence of the 3-kb STX16 deletion and AHO-like features and a clinical course complicated by concomitant 25-[OH]-vitamin D deficiency, which may have resulted, at least partly, from long-term use of antiepileptic drugs.

Section snippets

Case Report

A 17 year-old female patient was first admitted to our hospital with frequent absence seizures and hypocalcemia. The patient’s first episode as a tonic-clonic generalized seizure had occurred at the age of 14, at which time she was placed under treatment with valproate (3 × 500 mg). Although the patient was not compliant with the therapy for more than 1 week, she had a seizure-free period for 11 months. Subsequently, however, seizure episodes recurred and the patient was readmitted to the

Discussion

PHP refers to several distinct, but related, disorders in which end-organ resistance toward PTH is the most prominent feature. As a result of PTH resistance, patients with PHP have diminished serum concentrations of 1,25-[OH]2-vitamin D3, hypocalcemia, hyperphosphatemia, and increased PTH levels.

It has been documented that vitamin D deficiency can impair phosphaturic response to PTH.6., 12. Limited exposure to sunlight may have contributed to vitamin D deficiency in our patient.13 In addition,

Conclusion

Our findings correlate well with the previous reports regarding patients with AD-PHP-Ib. These include an increased fractional excretion of uric acid and hypouricemia, which has been reported previously only once in a kindred with this disorder. On the other hand, the presence of mild AHO-like features in the index case, whose diagnosis was confirmed by genetic analysis, raises the possibility that GNAS imprinting abnormalities might also lead to AHO features; however, it remains possible that

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