|Year : 2022 | Volume
| Issue : 2 | Page : 110-112
Pseudohypoparathyroidism: A Rare Cause of Status Epilepticus
Vinit Suri, Avinash Goswami, Shishir Pandey, Monika Goyal
Department of Neurology, Institute of Neurosciences, Indraprastha Apollo Hospital, New Delhi, India
|Date of Submission||28-Oct-2021|
|Date of Decision||01-Feb-2022|
|Date of Acceptance||02-Feb-2022|
|Date of Web Publication||21-Apr-2022|
D- 343, Defence Colony, New Delhi -110024
Source of Support: None, Conflict of Interest: None
Hypocalcemia can result in a variety of symptoms which include paresthesias, muscle spasms, cramps, tetany and circumoral numbness. Arrhythmias, heart failure and seizures constitute the serious symptoms arising from hypocalcemia. Seizures resulting from hypocalcemia are more common in the pediatric population. Although hypocalcemia can result from several causes, hypoparathyroidism and Vitamin D deficiency are most commonly encountered causes in clinical practice. Pseudohypoparathyroidism is a rare cause of hypocalcemia. We report a case of a young boy who presented to the emergency in status epilepticus with encephalopathy. ECG revealed prolonged QT interval which prompted further evaluation for a possible metabolic cause for this new onset status epilepticus. Routine laboratory investigations revealed hypocalcemia. A parathyroid pathology was suspected since phosphate level was elevated. Parathyroid hormone (PTH) levels were elevated suggesting PTH resistance pseudohypoparathyroidism which was diagnosed after exclusion of other causes of hypocalcemia and other acquired causes of PTH resistance. Patient was managed with intravenous calcium gluconate infusion, oral calcium supplementation, calcitriol and antiepileptic drugs.
Keywords: Hypocalcemia, pseudohypoparathyroidism, status epilepticus
|How to cite this article:|
Suri V, Goswami A, Pandey S, Goyal M. Pseudohypoparathyroidism: A Rare Cause of Status Epilepticus. Apollo Med 2022;19:110-2
| Introduction|| |
Hypocalcemia may result in a variety of symptoms including paresthesia's, muscle spasms, cramps, tetany, circumoral numbness, and serious symptoms including arrhythmia's, heart failure, and seizures. Seizures caused by hypocalcemia depend on the rate of reduction in serum calcium levels as well as the actual degree of hypocalcemia. According to the International League Against Epilepsy, a seizure can be attributed to an electrolyte abnormality if the electrolyte disturbance can be detected within 24 h of the seizure. Hypocalcemia has a variety of underlying causes including hypoparathyroidism, pseudohypoparathyroidism (PHP), Vitamin D deficiency, and adrenal failure. Vitamin D deficiency remains the most common cause. PHP is a rare cause of hypocalcemia attributed to parathyroid hormone (PTH) resistance and is diagnosed by excluding other causes and subtyped by genetic analysis.
| Case Report|| |
A 16-year-old boy presented with a 2-day history of self-limiting fever followed by increasing frequency of seizures over the next few days with 2–3 seizures per day despite two antiepileptic drugs including levetiracetam and valproate. He presented with five generalized tonic–clonic seizures over a 3-h period without consciousness between the episodes. He was product of consanguine marriage.
Examination revealed a comatose patient with normal, isocoric pupils with normal reaction to light, full external ocular movement, and normal fundi. Flexor motor responses in all four limbs with bilateral extensor plantar responses were elicitable without any meningeal signs.
Investigations revealed a prolonged QT interval on electrocardiogram [Figure 1] and severe hypocalcemia with serum calcium level of 5.1 mg/dl, and elevated serum phosphorus level of 5.4 mg/dl (2.5–4.5) suggestive of a parathyroid pathology caused by either hypoparathyroidism or parathyroid resistance. Serum PTH was. 105 pg/ml with low serum Vitamin D level of 7.10 ngm/ml and elevated serum alkaline phosphate level of 176 (25–125 mg/dl). Investigation to ruleout infective, autoimmune, vascular, and structural causes of seizures and brain imaging with contrast-enhanced magnetic resonance imaging brain and magnetic resonance venogram were normal. Cerebrospinal fluid examination revealed a cellular fluid with normal protein and sugar and negative meningoencephalitis and autoimmune encephalitis panel and negative cultures. Further investigations to identify the cause of severe hypocalcemia were conducted. To identify other causes of PTH resistance serum magnesium, Creatinine Phosphokinase (CPK) level and serum creatinine were evaluated and were observed to be normal. To further subclassify the PHP, the patient was examined for any evidence of Albright hereditary osteodystrophy (AHO) phenotype including short stature, dimple sign on hand, and mental retardation which were not observed though the patient had abdominal obesity. Noncontrast computed tomography of brain did not reveal the most specific feature of basal ganglionic calcification. X-ray examination of both hands did not reveal short 4th, 5th metacarpal, and moreover, X-ray examination of skull and pelvic X-rays were normal. Since the patient did not have a AHO phenotype, a provisional diagnosis of either PHP Type 1b or PHP Type 2 due to Vitamin D deficiency was considered. In PHP Type 2, role of severe Vitamin D deficiency is incriminated and Vitamin D supplementation should normalize phosphate uric action of PTH postVitamin D replacement. This response to Vitamin D supplementation was not observed in our patient who continued to have elevated serum phosphorus even 7 days postVitamin D supplementation suggesting a possibility of PHP Type 1b Ellsworth-Howard test or I. V PTH challenge test could have helped to further differentiate the two differentials of PHP type 2 or PHP type 1b but could not be conducted.
Differential diagnosis (if any)
- Vitamin D deficiency disease
- Postviral encephalitis.
The patient was managed with a combination of intravenous calcium gluconate infusion at 0.5 to1 mg/kg/h with titration of the rate of infusion according to the serum calcium levels which was monitored 6th hourly combined with oral calcium and calcitriol at 0.5 mg twice a day and gradually increased to 0.5 mg thrice a day. Antiepileptic drug therapy with levetiracetam.
Follow-up and outcomes
The patient responded well to treatment and discharged in stable condition. With advice monitoring every 3 monthly followed by yearly measurement of serum calcium, serum PTH, phosphorus and thyroid function as well as urinary calcium. The patient was lost to follow-up.
| Discussion|| |
Pseudohypoparathyroidism (PHP) is a rare genetic disorder where patient has features of hypoparathyroidism, hypocalcemia with hyperphosphatemia despite elevated parathyroid hormone levels. It results from unresponsiveness of peripheral organs to the action of PTH. A high PTH level is usually apparent in childhood at the age of 2-3 years and hypocalcemia is usually symptomatic in adolescent. Pseudohypoparathyroidism results in severe skeletal complications, attributed to the accompanying secondary hyperparathyroidism resulting from resistance of the renal receptors to the action of PTH resulting in reduction of bone density via exaggerated bone turnover. Elevated serum alkaline phosphatase can be a marker of PHP related bone disease and should warrant a thorough skeletal survey. PHP can be further subclassified into Type 1and 2. Type 2 PHP is rare and it is hypothesized to occur from a aquired defect due to Vitamin D deficiency which when replaced normalizes the phosphaturic response to PTH and serum phosphorus. To biochemically differentiate between Type1 and Type 2 PHP Ellsworth- Howard test is recommended. Type1 PHP is further classified into Type1a,1b,1c. Among the three Type1a and 1c have AHO phenotype and coexisting multiple hormone resistance. The most specific feature of AHO and was not observed in our patient. Other features include rounded faces, short stature, central obesity along with variable degree of mental retardation. Patients with PHP Type1b imprinting defect in maternal GNAS regulatory protein located in renal tubule is affected while skeletal GNAS is normal and they lack AHO phenotype. The overall goal of treatment of PHP is to maintain normal calcium, normal phosphorus, preventing hypercalciuria. Baseline bone densitometry is required to identify extent of any bone mineral loss. While there are numerous case reports addressing PHP in the paediatric population, there are only a few reports of PHP cases with a late presentation in adulthood. Our patient presented with an unrelated short duration febrile illness followed by serial seizures and status epilepticus, and investigations revealed hypocalcaemia with hyperphosphatemia due to pseudohypoparathyroidism which was diagnosed after eliminating other causes of hypocalcaemia. In addition, overlap vitamin D deficiency further intensified the hypocalcaemia.
Informed consent has been exempted as the patient was lost to follow-up.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Dr Vinit Suri had drafted the article, Dr. Avinash Goswami and Dr. Monika Goyal did the research work, Dr. Shishir Pandey did the editing, Dr. Kunal suri and Dr. Neelam Sahu helped in drafting the article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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