From the Department of Pediatrics, Kasturba Medical College, Mangalore, Karnataka 575 001, India.

Correspondence to: Sajitha S, Department of Pediatrics, University Medical Center, Dr. B.R. Ambedkar Circle, Mangalore, Karnataka 575 001, India. E-mail: [email protected]

Manuscript received: February 12, 2002;

Initial review completed: April 22, 2002;

Revision accepted: September 24, 2002.

Key words: Hypocalcemia, Serum parathormone.

Pseudohypoparathyroidism (PHP) is a term used to describe several related disorders characterised by end organ unresponsiveness to parathormone, due to receptor or post receptor defects. The characteristic biochemical derangements include hypocalcemia, hyperphosphatemia and high serum parathormone levels. A Medline search did not reveal any case report of PHP presenting as early onset neonatal hypocalcemia. We report a case of pseudohypoparathyroidism that presented in early neonatal period with hypocalcemic convulsions.

A 7-day-old male baby was referred to our neonatal unit, with history of multifocal clonic convulsions from 2nd day of life. He was the first baby of non-consanguineous parents. Parents were healthy with normal stature. Antenatal period was uneventful. Baby was born by vacuum extraction weighing 3.5 kg with Apgar score of 8 at 1’ and 10 at 5’. He was breastfed within one hour of delivery. Investigations in a local hospital revealed hypocalcemia for which calcium supplementation and intravenous phenobarbitone were given. As seizures persisted with 15-20 attacks per day, the baby was referred to our hospital.

On admission, the baby was irritable. Anterior fontanel was at level. Capillary filling time was more than 2 seconds. There were no dysmorphic features or skeletal malformations. Kidneys were not palpable. Urine output was 1mL/kg/h. The rest of the systemic examination was normal.

Investigations revealed normal blood glucose and low serum calcium 5.5 mg/dL. Septic screen including CSF analysis was negative. Blood urea was 40 mg/dL and serum creatinine was 1.2 mg%. Total protein and serum albumin was within normal limits. As seizures persisted, screening for metabolic disorders was done. Urine for metabolic screen was negative and serum ammonia was normal. ABG analysis showed normal pH and bicarbonate. Baby was started on calcium gluconate 75 mg/kg/day and intravenous phenobarbitone and phenytoin. The seizures persisted, and calcium remained low (6.2 mg/dL). Further investigations revealed serum phosphorous of 7.9 mg/dL (normal: 3.8 – 6.5 mg/dL) and alkaline phosphatase of 1053 IU/L (normal: 145-420 IU/L). Serum magnesium was 1.8 mg/dL (normal: 1.5-2.5 mg/dL). Ultrasound of abdomen did not reveal any abnormality. Blood urea and S. creatinine when repeated on fourth day of admission were 24 mg/dL and 0.6 mg/dL respectively. DTPA renal isotope scan showed normal renal function. The serum parathormone level by radioimmunoassay was 92 pg/mL (normal: 12-72 pg/mL), when serum calcium was 6.8 mg%. CT scan head was normal with no evidence of intracranial calcification. X-ray wrist did not reveal any shortening of metacarpals. Serum calcium, phosphorus and alkaline phosphatase of the mother were normal.

With evidence of persistent hypocalcemia, hyperphosphatemia, normal renal function and high serum parathormone levels, a diagnosis of PHP was made. The baby was treated with calcium supplementation and calcitriol 0.25 µg/day. Anticonvulsants were changed to carbamazepine. Within 1 week of starting calcitriol, serum calcium and phosphorus became normal. On follow up at 9 months, the baby was asymptomatic on calcitriol (0.25 µg/day) and calcium supplementation. Urine calcium to creatinine ratio was maintained within normal limits.

Pseudohypoparathyroidism is divided into 2 main types. Type I is characterised by low or absent renal CAMP production in response to parathormone (PTH). Type II responds to PTH with normal increase in urinary CAMP but show absent or subnormal phosphaturic response(1). Type I is further subdivided into 2 subtypes A and B. In type A that accounts for 60% of type I, the defect is localised to a subunit of GS protein(2). Most of these patients have distinctive morphological abnormalities collectively called "Albrights herediatry osteodystrophy". In this type hypocalcemia rarely develop before 3 years(3,4). In reported cases the age of onset of type II ranged from 1.8 - 70 yrs(3).

In the case described above, the baby presented in the early neonatal period with hypocalcemic convulsions. Predisposing factors of early onset hypocalcemia like prematurity, maternal diabetes or hyperparathyroidism, birth asphyxia etc were excluded. There was no evidence of hypomagnesemia or septicemia in the baby. Renal failure was excluded by normal renal isotope scan and renal function tests. Hypoparathyroidism (HP), which is more common in neonatal period, can also produce hypocalcemia and hyperphosphatemia. Serum parathormone levels are low or undetectable in HP while in PHP; the levels are elevated due to PTH resistance. There are few reports in neonates of transient PHP that presented as late onset hypocalcemia(5-6). In these patients PHP state was transient and resolved by 6 months of age. We tried weaning the child of calcitriol and calcium supplementation at 6 months, but restarted it as the baby developed hypocalcemia and hyperphosphatemia. At 9 months of age, on follow up, the present baby required calcitriol (0.25 µg/day 12 hrly) and calcium supplementation to maintain normal S. calcium and phosphorus. This baby needs further follow up to understand the course of the disease.

The main goal of therapy in these patients is to restore serum calcium and phosphorus as close to normal as possible. Replacement therapy with calcitrol combined with calcium supplementation and phosphorus restriction usually suffices to regulate blood calcium and phosphorus levels. These patients require regular monitoring of serum calcium, phosphorus, renal function tests and urinary calcium excretion by urinary calcium to creatinine ratio.

Contributors: PNK, UVS and SS were involved in the management of the patient and drafting of the manuscript. SS will act as the guarantor for the paper.

Funding: None.

Competing interests: None stated.

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