Correspondence and Reprint requests : Dr. Arvind Bagga, Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, Delhi-110029, India. Phone: 09868397543. Fax: 011-26588480 [DOI–10.1007/s12098–008–0187–2 [Received March 6, 2007; Accepted April 1, 2008] Clinical Brief Primary Hyperoxaluria Type 1 with a Novel Mutation Sidharth Kumar Sethi, Hans R. Waterham 1 , Sonika Sharma 2 , Alok Sharma 3 , Pankaj Hari and Arvind Bagga 2 Divisions of Pediatric Nephrology and Genetics, 3 Department of Pathology, All India Institute of Medical Sciences, New Delhi, 1 Lab. Genetic Metabolic Diseases*, Departments of Clinical Chemistry & Pediatrics, Academic Medical Centre, Amsterdam, The Netherlands ABSTRACT Primary hyperoxaluria type 1 [PH1] is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase AGT, which is encoded by the AGXT gene. We report an Indian family with two affected siblings having a novel mutation in the AGXT gene inherited from the parents. The index case progressed to end stage renal disease at 5 months of age. His 4 month old sibling is presently under follow up with preserved renal function. [Indian J Pediatr 2009; 76(2): 215-217] Email : arvindbagga@hotmail.com. Key words : Primary hyperoxaluria; Nephrocalcinosis Type 1 primary hyperoxaluria (PH1; OMIM 259900) is a life-threatening condition due to inherited deficiency of a liver-specific enzyme (alanine:glyoxylate aminotransferase, AGT) that causes impaired glyoxylate metabolism in peroxisomes of human hepatocytes. This disorder has an autosomal recessive inheritance and is characterized by marked hyperoxaluria, calcium oxalate urolithiasis or nephrocalcinosis and progressive loss of renal function. 1 Currently, there are a total of 55 AGXT gene sequence variants reported in the Human Gene Mutation Database [http://www.hgmd.cf.ac.uk/], 34 of which were missense or nonsense changes. 2 We report an Indian family with two affected siblings secondary to a novel inherited mutation in AGXT gene. This is the first report of a genetic study in an Indian family with PH1. CASE REPORTS Case 1 A 5-month-old was referred for evaluation of failure to thrive and episodes of cough and fast breathing. The child was a product of fourth degree consanguineous marriage. The child was the first in birth order. On examination, he weighed 7.0 Kg, head circumference was 39.6 cm and length was 55.0 cm. The respiratory rate was 62/ minute, pulse rate 110/ minute and blood pressure 100/70 mm Hg. The patient was pale; chest examination showed wheeze and fine crackles. Investigations showed hemoglobin level of 5 g/dl; blood level of urea was 119 mg/dl, creatinine 4.6 mg/dl, sodium 142 mEq/l, potassium 5.4 mEq/l, calcium 10 mg/dl, phosphate 6.9 mg/dl, alkaline phosphatase 460 IU/l, pH 7.27, pCO 2 19.8 mmHg and bicarbonate 11 mEq/l. Urinalysis was normal. Ultrasound of the abdomen revealed bilateral medullary nephrocalcinosis. Urinary oxalate excretion was 400 mg/ 1.73 m 2 per 24-hr (normal <40 mg/1.73 m 2 /24-hr). The child underwent peritoneal dialysis for metabolic acidosis, altered sensorium and uremia. Despite treatment, his condition deteriorated and he expired on day six of hospitalization because of worsening pneumonia. A post- mortem renal biopsy showed abundant oxalate crystals within the tubules (Fig. 1a), which had strong birefringence in polarized light (Fig. 1b). A diagnosis of PH1 was made in view of bilateral medullary nephrocalcinosis, raised urinary oxalate excretion and characteristic renal histology. Case 2 Five years later, this 4-month-old girl, sibling of the first patient presented with progressive facial puffiness of 1 month duration. She was third in birth order; an elder 3- year-old male sibling was reportedly healthy. On examination, this patient weighed 5 Kg, head circumference was 38.6 cm and length was 60 cm; systemic examination was normal. Investigations showed hemoglobin level of 11 g/dl; blood level of urea was 16 mg/dl, creatinine 0.5 mg/dl, sodium 148 mEq/l, Indian Journal of Pediatrics, Volume 76—February, 2009 215