Glutaric aciduria type I: A common cause of episodic encephalopathy and spastic paralysis in the Amish of Lancaster County, Pennsylvania

D. H. Morton, M. J. Bennett, L. E. Seargeant, C. A. Nichter, R. I. Kelley

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

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 unrecognized 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 μmol/liter (nl 0-5.6 μmol/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.

Original languageEnglish (US)
Pages (from-to)89-95
Number of pages7
JournalAmerican journal of medical genetics
Volume41
Issue number1
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Amish
  • cerebral palsy
  • glutaric acid
  • glutaryl coenzyme A dehydrogenase
  • metabolic encephalopathy
  • movement disorders
  • organic aciduria

ASJC Scopus subject areas

  • Genetics(clinical)

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