Neonatal pseudohypoparathyroidism
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《美国医学杂志》
1 Department of Pediatrics, University College of Medical Sciences and GTB Hospital,New Delhi, India
2 Department of Pathology, Sanjeevan Hospital, New Delhi, India
Abstract
The case of a neonate is presented who had early onset seizure associated with hypocalcemia, hyperphosphatemia, and raised parathyroid hormone. The infant did not have any stigmata of pseudohypoparathyroidism. The hypocalcemia was initially resistant to calcium therapy, but responded to vitamin D analog therapy. The diagnosis of 'neonatal pseudohypoparathyroidism' was entertained; the infant remained stable and seizure-free with normal serum biochemistry during 3 months of follow-up.
Keywords: Pseudohypoparathyroidism; Hypocalcaemic convulsions
Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biological activity of PTH.[1] A Medline search revealed very few case reports of PHP presenting as early onset neonatal hypocalcemia. We report a case of pseudohypoparathyroidism that presented in early neonatal period with hypocalcemic convulsions.
Case report
A four-day-old male neonate presented with a history of multiple episodes of clonic convulsions since the second day of life. The child, born to a 25-years-old primigravida at term, cried soon after birth and was on exclusive breast feeds. The parents were healthy with normal stature and without any history of consanguinity. Antenatal period was uneventful.
The baby weighed 2.8 kg, with head circumference of 34 cm. Anterior fontanelle was at level and there was no dysmorphic facies or gross congenital malformation. Urine output was 1 ml/kg/h. Rest of the systemic examination revealed no abnormality.
Provisional diagnosis of metabolic seizure was made and investigations revealed blood glucose 87 mg/dL and serum calcium 6.2 mg/dL. Blood urea was 44 mg/dL and septic screen including CSF analysis was negative. Ultrasound skull and abdomen did not reveal any abnormality. In view of hypocalcaemia, the child was started on i.v. calcium gluconate. Persistence of seizure led to metabolic screening which revealed normal serum ammonia and ABG analysis. Further investigations revealed serum calcium - 5.9 mg/dL, serum phosphorus - 8.5 mg/dL (normal: 3.8-6.5 mg/dL) and alkaline phosphatase of 926 IU/l (normal 150-400 IU/l). Serum magnesium was within normal limits. Repeat blood urea was 32 mg/dl and serum creatinine, 0.8 mg/dL. The serum parathormone levels by radioimmunoasssay was 114 pg/mL (normal: 10-70 pg/mL), when serum calcium was 6.2 mg/dL. No abnormality was noticed on CT scan head. Serum calcium, phosphorus and alkaline phosphatase of mother were normal.
In view of persistent hypocalemia, hyperphosphatemia and high serum parathormone levels, diagnosis of PHP was made, and the child was treated with calcium supplementation and calcitriol 0.25 μg/day. Serum calcium and phosphorus became normal within 15 day of starting calcitriol. On follow -up at 3 months, the child was asymptomatic on calcitriol and calcium supplementation.
Discussion
In 1942, Fuller Albright first introduced the term pseudohypoparathyroidism to describe patients who presented with PTH-resistant hypocalcemia and hyperphosphatemia. In PHP, the parathyroid glands are normal or hyperplastic histologically, and neither endogenous nor administered PTH raises the serum levels of calcium or lowers the level of phosphorus.
Pseudohypoparathyroidism is divided into 2 main types. Type I is characterized by low or absent renal cyclic adenosine monophosphate (CAMP) production in response to parathormone (PTH). Type II responds to PTH with normal increase in urinary CAMP but shows absent or subnormal phosphaturic response[2]. Type I is further subdivided into 2 subtypes, A and B. In sub type A, the affected patients have a genetic defect of the a subunit of the stimulatory guanine nucleotide binding protein (GSa), with most of them having distinctive morphological abnormalities collectively called "Albrights herediatry osteodystrophy".[1] In this type, hypocalcemia rarely develops before 3 years.[3] Subtype I B patients have normal levels of G protein activity with defect in PTH receptor expression or a defect in catalytic subunit of adenyl cyclase.
In the present case, the baby presented in the early neonatal period with hypocalcemic convulsions which were resistant to i.v. calcium gluconate. Hypomagnesemia, septicemia, renal failure were ruled out. There were no predisposing factors of early onset hypocalcemia like prematurity, birth asphyxia. Elevated levels of serum parathormone levels further ruled out hypoparathyroidism. Few case reports of transient PHP that presented as late onset hypocalcemia are available in the literature[4],[5] but to the best of our knowledge there is only one case report in literature of pseudohypoparathyrisdism presenting as early onset hypocalcaemia[6]. At 3 months of age, the child was on oral calcium supplementation and calcitriol and was seizure free.
All patients with severe symptomatic hypocalcemia should be initially treated with intravenous calcium. Administration of oral calcium and 1 alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of PHP. The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalciuria and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP could cause increased bone remodeling and can lead to hyperparathyroid bone disease.
References
1. DiGeorge AM. Pseudohypothyroidism. In Behrman Er, Kliegmann RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 16th edn. Philadelphia; WB Saunders Co, 2000; 1718-1719.
2. Vasicek TJ, Mc Devitt Be, Freeman MW, Fennick BJ, Hendy GH, Potts J et al . Nucleotide sequence of human PTH gene. Proc Natl Acad Sci USA 1983; 80: 2127-2131.
3. Drezner MK, Neelson FA. Pseudohypoparathyroidism. In Stanbury JB, Wyngaarden JB, Friderickson DS, eds. The metabolic basis of inherited disease. New York; Mc Graw-Hill, 1983; 1508-1527.
4. Manzar S. Transient pseudohypoparathyroidism and neonatal seizure. J Trop Pediatr 2001; 47: 113-114.
5. Minagawa M, Yasuda T, Kobayashi Y, Niimi H. Transient pseudohypoparathyroidism in neonate. Eur J Endocrinol 1995; 133: 151-155.
6. Sajitha S, Krishnamoorthy PN, Shenoy UV. Pseudohypoparathyroidism in Newborn - A Rare Presentation. Indian Pediatrics 2003; 40: 47-49.(Narang Manish, Salota Ras)
2 Department of Pathology, Sanjeevan Hospital, New Delhi, India
Abstract
The case of a neonate is presented who had early onset seizure associated with hypocalcemia, hyperphosphatemia, and raised parathyroid hormone. The infant did not have any stigmata of pseudohypoparathyroidism. The hypocalcemia was initially resistant to calcium therapy, but responded to vitamin D analog therapy. The diagnosis of 'neonatal pseudohypoparathyroidism' was entertained; the infant remained stable and seizure-free with normal serum biochemistry during 3 months of follow-up.
Keywords: Pseudohypoparathyroidism; Hypocalcaemic convulsions
Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biological activity of PTH.[1] A Medline search revealed very few case reports of PHP presenting as early onset neonatal hypocalcemia. We report a case of pseudohypoparathyroidism that presented in early neonatal period with hypocalcemic convulsions.
Case report
A four-day-old male neonate presented with a history of multiple episodes of clonic convulsions since the second day of life. The child, born to a 25-years-old primigravida at term, cried soon after birth and was on exclusive breast feeds. The parents were healthy with normal stature and without any history of consanguinity. Antenatal period was uneventful.
The baby weighed 2.8 kg, with head circumference of 34 cm. Anterior fontanelle was at level and there was no dysmorphic facies or gross congenital malformation. Urine output was 1 ml/kg/h. Rest of the systemic examination revealed no abnormality.
Provisional diagnosis of metabolic seizure was made and investigations revealed blood glucose 87 mg/dL and serum calcium 6.2 mg/dL. Blood urea was 44 mg/dL and septic screen including CSF analysis was negative. Ultrasound skull and abdomen did not reveal any abnormality. In view of hypocalcaemia, the child was started on i.v. calcium gluconate. Persistence of seizure led to metabolic screening which revealed normal serum ammonia and ABG analysis. Further investigations revealed serum calcium - 5.9 mg/dL, serum phosphorus - 8.5 mg/dL (normal: 3.8-6.5 mg/dL) and alkaline phosphatase of 926 IU/l (normal 150-400 IU/l). Serum magnesium was within normal limits. Repeat blood urea was 32 mg/dl and serum creatinine, 0.8 mg/dL. The serum parathormone levels by radioimmunoasssay was 114 pg/mL (normal: 10-70 pg/mL), when serum calcium was 6.2 mg/dL. No abnormality was noticed on CT scan head. Serum calcium, phosphorus and alkaline phosphatase of mother were normal.
In view of persistent hypocalemia, hyperphosphatemia and high serum parathormone levels, diagnosis of PHP was made, and the child was treated with calcium supplementation and calcitriol 0.25 μg/day. Serum calcium and phosphorus became normal within 15 day of starting calcitriol. On follow -up at 3 months, the child was asymptomatic on calcitriol and calcium supplementation.
Discussion
In 1942, Fuller Albright first introduced the term pseudohypoparathyroidism to describe patients who presented with PTH-resistant hypocalcemia and hyperphosphatemia. In PHP, the parathyroid glands are normal or hyperplastic histologically, and neither endogenous nor administered PTH raises the serum levels of calcium or lowers the level of phosphorus.
Pseudohypoparathyroidism is divided into 2 main types. Type I is characterized by low or absent renal cyclic adenosine monophosphate (CAMP) production in response to parathormone (PTH). Type II responds to PTH with normal increase in urinary CAMP but shows absent or subnormal phosphaturic response[2]. Type I is further subdivided into 2 subtypes, A and B. In sub type A, the affected patients have a genetic defect of the a subunit of the stimulatory guanine nucleotide binding protein (GSa), with most of them having distinctive morphological abnormalities collectively called "Albrights herediatry osteodystrophy".[1] In this type, hypocalcemia rarely develops before 3 years.[3] Subtype I B patients have normal levels of G protein activity with defect in PTH receptor expression or a defect in catalytic subunit of adenyl cyclase.
In the present case, the baby presented in the early neonatal period with hypocalcemic convulsions which were resistant to i.v. calcium gluconate. Hypomagnesemia, septicemia, renal failure were ruled out. There were no predisposing factors of early onset hypocalcemia like prematurity, birth asphyxia. Elevated levels of serum parathormone levels further ruled out hypoparathyroidism. Few case reports of transient PHP that presented as late onset hypocalcemia are available in the literature[4],[5] but to the best of our knowledge there is only one case report in literature of pseudohypoparathyrisdism presenting as early onset hypocalcaemia[6]. At 3 months of age, the child was on oral calcium supplementation and calcitriol and was seizure free.
All patients with severe symptomatic hypocalcemia should be initially treated with intravenous calcium. Administration of oral calcium and 1 alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of PHP. The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalciuria and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP could cause increased bone remodeling and can lead to hyperparathyroid bone disease.
References
1. DiGeorge AM. Pseudohypothyroidism. In Behrman Er, Kliegmann RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 16th edn. Philadelphia; WB Saunders Co, 2000; 1718-1719.
2. Vasicek TJ, Mc Devitt Be, Freeman MW, Fennick BJ, Hendy GH, Potts J et al . Nucleotide sequence of human PTH gene. Proc Natl Acad Sci USA 1983; 80: 2127-2131.
3. Drezner MK, Neelson FA. Pseudohypoparathyroidism. In Stanbury JB, Wyngaarden JB, Friderickson DS, eds. The metabolic basis of inherited disease. New York; Mc Graw-Hill, 1983; 1508-1527.
4. Manzar S. Transient pseudohypoparathyroidism and neonatal seizure. J Trop Pediatr 2001; 47: 113-114.
5. Minagawa M, Yasuda T, Kobayashi Y, Niimi H. Transient pseudohypoparathyroidism in neonate. Eur J Endocrinol 1995; 133: 151-155.
6. Sajitha S, Krishnamoorthy PN, Shenoy UV. Pseudohypoparathyroidism in Newborn - A Rare Presentation. Indian Pediatrics 2003; 40: 47-49.(Narang Manish, Salota Ras)