2020 Volume 52 Issue 1 Pages 34-37
Glutaric aciduria type 1 (GA1) is a metabolic disorder caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Most patients develop an acute encephalopathic crisis in early childhood, and present severe involuntary movements like dystonia. Herein, we present a female patient with GA1 who showed megalencephaly and moderate intellectual disability, but no encephalopathic crisis. A brain MRI showed white matter degeneration and hypoplasia of the bilateral temporal lobes. The diagnosis of GA1 was confirmed biochemically by urine organic acid analysis. GCDH gene analysis showed c.914C>T (p. Ser305Leu) & c.1016T>G (p.Met339Arg) known compound heterozygous mutations. Typically, patients with “late-onset type” GA1 are rarely reported. These patients present neither encephalopathic crisis nor involuntary movements in early childhood. However, they do develop non-specific neurological symptoms including headache, dizziness, tremor, cognitive dysfunction, spastic paralysis, and urinary incontinence in adolescence and adulthood. As GA1 phenotypes are not correlated with residual GCDH activity or genotypes, it is not known why these patients do not suffer from acute encephalopathy. Early diagnosis is as important for patients with the late-onset type GA1 as it is acute-onset type GA1 because administration of carnitine and the restriction of excess protein intake may improve symptoms. In Japan, newborn screening for GA1 began in 2011. Therefore, it is important to consider the diagnosis of the late-onset type GA1 and analyze urine organic acid in patients born before 2011 who present non-specific neurological symptoms and white matter degeneration with hypoplasia of the bilateral temporal lobes.
