Anurag Bajpai

Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials

Acanthamoeba was implicated as the causative agent of chronic meningitis in three apparently immunocompetent children. Diagnosis was established by cerebrospinal fluid wet mount examination and culture. Two children improved rapidly with combination oral therapy composed of trimethoprim-sulfamethoxazole, rifampin and ketoconazole.

Approach to renal tubular disorders

The renal tubule plays an important role in fluid and electrolyte homeostasis. Renal tubular disorders may affect multiple (e.g., Fanconi syndrome) or specific (e.g., nephrogenic diabetes insipidus, renal glucosuria) tubular functions. Most conditions are primary and monogenic but occasionally are secondary to other disorders (focal segmentai glomerulosclerosis, cystinosis, Lowe syndrome). Tubular dysfunction should be considered in all children with failure to thrive, polyuria, refractory rickets, hypokalemia and metabolic acidosis. Careful clinical and laboratory evaluation is essential for appropriate diagnosis and specific management of these conditions.

Intravenous pamidronate therapy in osteogenesis imperfecta: response to treatment and factors influencing outcome.

Pamidronate treatment has been shown to improve outcome in osteogenesis imperfecta (OI); however, factors influencing outcome are unclear. The present study was conducted to evaluate the response to pamidronate therapy with special emphasis on factors influencing outcome. Twenty children with OI treated with pamidronate were evaluated in a prospective, open clinical trial. Pamidronate (9 mg · kg−1 · yr−1) was administered intravenously at the age of 4.5 ± 4.2 years for 2.9 ± 0.7 years (range, 2-3.8 years). Treatment led to increase in bone mineral density (BMD) Z score by 0.7 ± 0.3 every year resulting in significant improvement in BMD Z score (from −4.6 ± 1.1 to −2.5 ± 1.1, P < 0.001). BMD Z score was within the reference range (>−2) in 9 subjects (45%) at the last follow-up as against none at initiation of treatment (P < 0.001). Fracture rate decreased significantly during treatment (3.3 ± 1.4 to 0.8 ± 0.9, P < 0.001) with 8 subjects (40%) having no fracture during the treatment period. Significantly greater proportion (88.2%) of children were able to walk at last follow-up compared with those at initiation of treatment (45.4%). Increase in BMD Z score and final BMD Z score was not influenced by age at initiation of treatment, duration of treatment, or initial BMD Z score. Treatment before infancy (n = 7) was associated with higher final subjective score (6.3 ± 0.5 vs 4.9 ± 1.5, P = 0.03). Our study reiterates the efficacy of pamidronate in OI. The poorer response of our subjects may be related to compromised calcium and vitamin D status.

Hypocalcemic heart failure masquerading as dilated cardiomyopathy

Hypocalcemia is a rare, but reversible, cause of congestive heart failure. We report a 4-month-old boy diagnosed as dilated cardiomyopathy who had prolonged QOTC with low blood levels of calcium, normal phosphate, elevated alkaline phosphatase and findings suggestive of rickets. In view of non response to calcium and vitamin D3, a possible diagnosis of VDDR I (Vitamin Ddependent rickets) was made and he was treated with calcium and calcitriol. The serum calcium levels normalised within 10 days, along with resolution of the signs and symptoms of heart failure, near normal left ventricular function and normalisation of QOTC. Pediatricians should be aware of the association of hypocalcemia with cardiac dysfunction and should keep it as a possible reversible cause of heart failure in children.

Growth Hormone Therapy

Growth hormone (GH) therapy has revolutionized treatment of children with growth hormone deficiency (GHD). Improved height outcome with final height in the target height range has been achieved in these children. Identification of Creutzfeldt-Jakob disease, a deadly prion mediated disorder, in recipients of pituitary GH accelerated the transition from pituitary derived GH to recombinant GH. Once daily subcutaneous administration of the freeze-dried preparation at evening is the recommended mode of GH therapy. Studies have led to use of higher dose of GH for improving height outcome (0.33 mg/kg/week or 0.14 IU/kg/day) albeit at a significantly high cost. Growth velocity increases from 3–4 cm/year before therapy to 10–12 cm/year during the first two years of therapy and is maintained at 7–8 cm/year after a period of two years. Close follow-up with regular clinical and laboratory monitoring is essential for achieving a desirable height outcome. A theoretical unlimited supply has led to wide spread use of GH in a variety of disorders other than GHD. Initially started in children with Turner syndrome, GH has now been used in chronic renal failure, idiopathic short stature and intrauterine growth restriction besides a wide array of newly emerging indications.

Ovarian Cysts in Young Girls with Hypothyroidism: Follow-up and Effect of Treatment

Ovarian cysts have been reported in girls with longstanding uncompensated primary hypothyroidism. Restoration of euthyroid state has been associated with resolution of these cysts; long-term follow-up of these patients is however lacking. We evaluated the outcome in ten girls with ovarian cysts and hypothyroidism managed at our hospital with special emphasis on subsequent pubertal development and ovarian imaging. Patients were diagnosed at the age of 8.6 +/- 2.3 years (mean +/- SD) with severe uncompensated primary hypothyroidism (TSH levels >100 mIU/l in all; 509.3 +/- 651 mIU/l) and growth retardation (height SDS -4.1 +/- 1.8). Nine girls had vaginal bleeding at diagnosis; five also had thelarche. LH and FSH levels were prepubertal in all patients. Ovarian cysts were bilateral in eight girls (80%); internal septation was noted in six. Thyroxine replacement (4.1 +/- 0.7 microg/kg/day) led to normalization of TSH levels with reversal of pubertal changes and regression of ovarian cysts in all patients 2.2 +/- 1.0 months after treatment. At last follow-up 3.5 +/- 2.6 years after initiation of treatment at the age of 12.0 +/- 2.3 years, all patients had normal ovarian size in ultrasound evaluation with six girls progressing to normal puberty. Our study emphasizes the need to exclude hypothyroidism in young girls with ovarian cysts. Identification of hypothyroidism in these girls obviates the need for extensive investigations.

Pseudohypoparathyroidism Presenting with Bony Deformities Resembling Rickets

Pseudohypoparathyroidism (PHP), characterized by hypocalcemia, hyperphosphatemia and elevated parathormone level, may rarely be associated with bony deformities resembling rickets. The authors report two siblings with clinical and radiological features suggestive of rickets unresponsive to treatment with vitamin D. Low serum calcium, elevated serum phosphate, normal renal functions, raised tubular maximum of phosphate and high serum parathormone were suggestive of PHP. Treatment with 1-hydroxyvitamin D and calcium carbonate led to decrease in bone pain, increase in height and weight and resolution of radiological features. PHP should be suspected in patients with bony deformities, hypocalcemia, elevated blood phosphate levels and normal renal functions

Nephrogenic diabetes insipidus presenting with developmental delay and intracranial calcification

A one-year-boy presented with constipation, fever, failure to thrive and developmental delay from the neonatal period. Investigations revealed persistent hypernatremia and deranged renal functions. Diagnostic work-up was suggestive of nephrogenic diabetes insipidus (NDI). Computerized tomography of head revealed calcification in the frontal, thalamic and basal ganglia region. The rare association of NDI and intracranial calcification is discussed

Combination Growth Hormone and Gonadotropin Releasing Hormone Analog Therapy in 11β-Hydroxylase Deficiency

Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

CNS germinoma in a boy with simple virilizing 21-hydroxylase deficiency and precocious puberty.

A 6 year-old boy presented with peripheral precocious puberty and was diagnosed as having simple virilizing 21-hydroxylase deficiency based on clinical features and elevated 17-hydroxyprogesterone levels on ACTH stimulation. He was managed with glucocorticoids and mineralocorticoids. Two years later he presented with features of CNS involvement in the form of seizures and raised intracranial pressure with rapid progression of puberty. Contrast enhanced CT scan of brain showed an intraventricular tumor with cerebrospinal fluid cytology suggestive of germinoma. Serum and CSF levels of human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) were elevated, confirming the diagnosis of germinoma.