M P Desai1, J V Khatri. 1. Department of Pediatrics, Sir Hurkisondas Nurrotumdas Hospital and Research Center, Bombay.
Abstract
OBJECTIVE: To study the nature and clinical course of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) due to nesidioblastosis. DESIGN: Clinical, laboratory and therapeutic evaluation of infants with this disorder and study the outcome. SETTING: Hospital born neonates and infants referred from other hospitals. SUBJECTS: Thirteen infants from 9 families inclusive of four pairs of siblings referred within few hours of birth to 3 months of age, for seizures. Mean birth weight was 3.68 +/- 0.45 kg. Consanguinity documented in one sporadic and one familial case. METHODS: Clinical and laboratory evaluation by standard biochemical and radioimmunoassay techniques. RESULTS: The mean serum insulin level of 24.2 +/- 12.5 mIU/ml was in the normal range but inappropriately high for the corresponding hypoglycemic blood sugar (23.1 +/- 9.1 mg/dl) value, with an I/G ratio of 1.36 +/- 0.97; as in hyperinsulinemia (normal < 0.4). Investigations excluded other causes of persistent hypoglycemia. A trial of i.v./oral glucose, frequent carbohydrate rich feeds in all, oral diazoxide (10 to 20 mg/kg) in 9/13 cases along with subcutaneous octreotide (20 micrograms/kg QID) in one helped, but pancreatic resection (85 to 90%) was opted for in two (1 familial, 1 sporadic). Six infants including one with pancreatic resection succumbed to hypoglycemia (n = 1) or fulminating infection (n = 3) or brain damage. Of the seven survivors, one familial case with pancreatic resection is brain damaged, and of the six on diazoxide therapy, one is slightly subnormal while one sporadic and three familial cases have done well. One infant was lost to follow up. Diazoxide could be withdrawn in two subjects (1 familial, 1 sporadic) by 8 years of age signifying maturation of islet cell function. CONCLUSION: PHHI appropriately known as 'Islet cell dysmaturation syndrome' is a complex disorder posing problems in diagnosis and therapy. The high familial incidence (77%), with intrafamilial variation in the severity, insulin levels in the normal range but in appropriately high for the blood glucose levels, normal C-peptide levels, with normal I/G ratio (< 0.4) in 4/13 are some of the notable features of this study. Severe recurrent infections in nearly 30%, is an unusual feature in this series and needs an indepth study. The mortality (46%) and morbidity (43%) in survivors is high and calls for greater awareness, early diagnosis and genetic counselling, as this disorder may be familial.
OBJECTIVE: To study the nature and clinical course of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) due to nesidioblastosis. DESIGN: Clinical, laboratory and therapeutic evaluation of infants with this disorder and study the outcome. SETTING: Hospital born neonates and infants referred from other hospitals. SUBJECTS: Thirteen infants from 9 families inclusive of four pairs of siblings referred within few hours of birth to 3 months of age, for seizures. Mean birth weight was 3.68 +/- 0.45 kg. Consanguinity documented in one sporadic and one familial case. METHODS: Clinical and laboratory evaluation by standard biochemical and radioimmunoassay techniques. RESULTS: The mean serum insulin level of 24.2 +/- 12.5 mIU/ml was in the normal range but inappropriately high for the corresponding hypoglycemic blood sugar (23.1 +/- 9.1 mg/dl) value, with an I/G ratio of 1.36 +/- 0.97; as in hyperinsulinemia (normal < 0.4). Investigations excluded other causes of persistent hypoglycemia. A trial of i.v./oral glucose, frequent carbohydrate rich feeds in all, oral diazoxide (10 to 20 mg/kg) in 9/13 cases along with subcutaneous octreotide (20 micrograms/kg QID) in one helped, but pancreatic resection (85 to 90%) was opted for in two (1 familial, 1 sporadic). Six infants including one with pancreatic resection succumbed to hypoglycemia (n = 1) or fulminating infection (n = 3) or brain damage. Of the seven survivors, one familial case with pancreatic resection is brain damaged, and of the six on diazoxide therapy, one is slightly subnormal while one sporadic and three familial cases have done well. One infant was lost to follow up. Diazoxide could be withdrawn in two subjects (1 familial, 1 sporadic) by 8 years of age signifying maturation of islet cell function. CONCLUSION:PHHI appropriately known as 'Islet cell dysmaturation syndrome' is a complex disorder posing problems in diagnosis and therapy. The high familial incidence (77%), with intrafamilial variation in the severity, insulin levels in the normal range but in appropriately high for the blood glucose levels, normal C-peptide levels, with normal I/G ratio (< 0.4) in 4/13 are some of the notable features of this study. Severe recurrent infections in nearly 30%, is an unusual feature in this series and needs an indepth study. The mortality (46%) and morbidity (43%) in survivors is high and calls for greater awareness, early diagnosis and genetic counselling, as this disorder may be familial.