GLUTARIC ACIDURIA TYPE-I - A COMMON CAUSE OF EPISODIC ENCEPHALOPATHY AND SPASTIC PARALYSIS IN THE AMISH OF LANCASTER COUNTY, PENNSYLVANIA

We have diagnosed type I glutaric aciduria (GA-I) in 14 children from 7 Old Order Amish families in Lancaster County, Pennsylvania. An otherwise rare disorder, GA-I appears to be a common cause of acute encephalopathy and cerebral palsy among the Amish. The natural history of the disease, which was previously unreconnized in this population, is remarkably variable and ranges from acute infantile encephalopathy and sudden death to static extrapyramidal cerebral palsy to normal adult. Ten patients first manifested the disease between 3 and 18 months at the time of an acute infectious illness. Four of these children died in early childhood, also during acute illnesses. However, there has been little progression of the neurological disease after age 5 years in the surviving children and intellect usually has been preserved, even in children with severe spastic paralysis. When well, patients have plasma glutaric acid concentrations ranging from 4.8 to 14.2-mu-mol/liter (nl 0-5.6-mu-mol/liter) and urinary glutaric acid concentrations from 12.5 to 196 mg/g creatinine (nl 0.5-8.4 mg/g creatinine). We have found that GA-I can be diagnosed in the Amish by measurement of urinary glutaric acid concentrations using isotope-dilution gas chromatography/mass spectrometry, whereas the diagnosis can easily be missed by routine urine organic acid gas chromatography. Based on our observations about the natural history of GA-I in the Amish, we anticipate that, with early diagnosis afforded by GC/MS screening of individuals at risk, the combination of restriction of dietary protein and limitation of protein catabolism, dehydration, and acidosis during illnesses will prevent the onset or progression of neurological disease in Amish patients with this variant of GA-I.