878 Failure to Isolate a Transmissable Agent From the Pancreas of a Child With Newly Diagnosed Diabetes Mellitus

Abstract

Muscle C m n i t i n e Deficiency i n a P a t i e n t with 877 1 P e r s i s t e n t N-tal Diabetes and Hypokalemia.J. McLAUGHLIN, P. OZAND, L. KOSKI, N. MACUREN*, M. GUMBINAS, R. BWAR and M. CORNBLATH, Baltimore, MD A 3 year old Cuban female with p e r s i s t e n t neonatal diabete m e l l i t u s developed corneal o p a c i t i e s , photophobia, hirsuitism and f a i l u r e t o t h r i v e following a prolonged episode of hypoglycemia with coma and s e i z u r e a t 8 months of age. Generalized myopathy with marked proximal muscle weakness was noted a t 2 years of age. P e r s i s t e n t hypokalemia was noted from 2% years o age. Electromyography and nemre conduction v e l o c i t i e s a t 3 years of age showed mild non-specific changes but t h e creatinephosphokinase was elevated a t 197mU/ml (N<45mU/ml) and t h e muscle biopsy showed increased i n t r a f i b e r (type L f i b e r s ) f a t droplets. The serum c a r n i t i n e was normal a t 79.2vM/L (mean of 26 age control s e r a 53f21~M/L) but t h e muscle f r e e c a r n i t i n e an s h o r t chain a c y l c a r n i t i n e were markedly reduced a t 0.29 (N>1.6 and 0.09 (N>1.1) yM/gm muscle respectively. Additionally hyper aldasteronism and hyperreninemia were a l s o noted i n face of a normal blood pressure.This case appears t o show a previously undescribed associa t i o n between i n s u l i n r e q u i r i n g diabetes and muscle c a r n i t i n e deficiency. An underlying defect of c e l l u l a r membrane transpor involving muscle, cornea and perhaps pancreatic 6 c e l l s is suggested by t h e findings. Supported NIH g r a n t s A.M. 19256 I A 9 year old g i r l died i n ketoacidotic coma t h a t developed I l e s s than two weeks a f t e r her f i r s t symptoms of diabetes me1 l i tus . Electron microscopic examination of pancreatic t i s s u e showed acute beta c e l l necrosis associated with myxoparawxovirus-like p a r t i c l e s in i s l e t , acinar and ductal c e l l s . W e attempted t o i s o l a t e a virus from the pancreas of t h i s p a t i e n t by several techniques. Primary inoculation and passageof pancreas onto Hep 2 , cerco (CMK) and rhesus monkey kidney, and human embryonic lung (HEL) t i s s u e c u l t u r e were negative f o r cytopathic e f f e c t (CPE), hemadsorption with guinea pig red blood c e l l s (HA), challenge with echovirus 11 and electron microscopy (EM). HnCl2, then centrifuged a t 10,000 xg f o r 10 min. The supernatanl f r a c t i o n s were assayed f o r FDPase a c t i v i t y using f ructose-1,6-diphosphate a s s u b s t r a t e . The hydrolyzed phosphate was estimatec by the method of Fiske and SubbaRow. Extracts from normal human placentas hydrolze 1.5 u M phosphate/mg protein/hr. In order t o a s c e r t a i n t h a t the phospFate hydrolyzed i s from Fructose-1,6-diphosphate, a labeled s u b s t r a t e U-( 1 4~) -~r u c t o s e -l , 6 -d iphosphate was used and the hydrolysis products were determined by t h i n layer chromotography using 80% propanol a s solvent. Full term placental e x t r ...