Volume 4 - Issue 1
Department of Pediatrics, Kauvery Hospital, Trichy, India
Pseudohypoparathyroidism, a rare hereditary endocrine disorder, characterized by peripheral resistance to Parathormone (PTH) and preserved renal function, presents with hypocalcemia and hyperphosphatemia, along with high levels of PTH. This entity varies from hypoparathyroidism, where hypocalcemia results from low levels of PTH.
An 8-months-old, developmentally normal, boy presented with multiple episodes of seizure in a day, each lasting less than 5 min, with no history of fever, vomiting, irritability. Antenatal and birth history were uneventful.
He had his first seizure at five months of age, and on evaluation was found to have hepatosplenomegaly and hypocalcemia (calcium, 4.85 mg/dl). On further workup, serum phosphorus was 6.3, Magnesium, 1.5 mg/dl, markedly elevated levels of Alkaline phosphatase at 553; and PTH, 329.8. Vitamin D3 was 28.38 (insufficient). Serum TSH was normal. Serum calcium improved (5.99 mg/dl) after IV calcium correction. He was discharged with the advice to take antiepileptics, calcium and Vitamin D3 supplements.
He had required another admission for similar presentation at 6 months of age.
On examination, he was drowsy, had pallor, hepatosplenomegaly,and a full anterior fontanelle. Weight was 7 kg and height 68 cm, belonging to 1st-3rd centile and 3rd-50th centile. General examination revealed a round face with brachydactyly, and a dimple noted at the base of 3rd finger. Laboratory investigations confirmed the presence of hypocalcemia (calcium, 5.06 mg/dl), high normal phosphorus (6 mg/dl) and elevated PTH (85.2) and ALP (861) with serum Vitamin D3 level being 20.99 ng/ml.
Serial calcium level following parenteral calcium administration was 6.4 mg/dl. X-ray of wrist joint revealed advanced bone age with short 4th-5th metacarpals. USG abdomen done in view of hepatosplenomegaly was normal. MRI Brain was normal.
Persistent hypocalcemia, hyperphosphatemia with elevated PTH and insufficient Vitamin D3 with radiological evidence of advanced bone age clinched the diagnosis of pseudohypoparathyroidism with possibility of Albright's hereditary osteodystrophy.
PTH levels monitored before and after IV calcium correction were 85.2 and 158.4, respectively. After a discussion with endocrinologist, Inj. Vitamin D 3 lakh IU was given parenterally. Repeat serum calcium was still on the lower side (5.54). IV calcium was restarted. He was seizure free and his sensorium improved.
Genetic testing confirmed the diagnosis. As per parents' wishes, he was referred to ICH Chennai.
Pseudohypoparathyroidism can present with hypocalcaemic seizure. Incidence is reported to be 0.3-1.1/100000 population. It is classified into various types, Type 1 and 2. Type 1 again classified into a, b, and c .
Albright was the first person to describe a syndrome of short stature, round face, obesity, brachydactyly and heterotopic ossifications in association with pseudohypoparathyroidism. It is caused by a genetic mutation involving GNAS. Type 1a is associated with Albright's hereditary osteodystrophy (AHO). Patients also present with resistance to other hormones leading to hypothyroidism, hypogonadism and growth hormone deficiency .
Short fourth and/or fifth metacarpals present as dimpling over the respective knuckles, also called 'Archibald sign.' Roentgenography may also reveal short metacarpals, metatarsals, distal phalanges of thumbs, advanced bone age, and ectopic ossification Skeletal maturation should be monitored with roentgenography of the left hand at regular intervals .
Life expectancy is usually normal in patients with AHO. Severe-morbid obesity with associated complications such as obstructive sleep apnea, neuropsychiatric disorders, seizures, and cataracts are more common in AHO associated with PHP1A .
Senior Consultant Paediatrician (Head - Academics)