Table 4b.

Genes of Interest in the Differential Diagnosis of a Symptomatic Individual with Findings Suggestive of Late-Onset or Untreated Infantile-Onset Classic Isovaleric Acidemia

Gene(s)DisorderMOILaboratory FindingsClinical Findings
GCDH Glutaric acidemia type 1 ARMetabolic acidosis 1, 2
  • Acute encephalopathic crises
  • Macrocephaly
  • Seizures
MCEE
MMAA
MMAB
MMADHC
MMUT 		Isolated methylmalonic acidemia AR
  • Metabolic acidosis
  • Hyperammonemia
  • Methylmalonic acid in urine
  • Propionylcarnitine on acylcarnitine analysis 1, 3
  • Metabolic decompensations
  • Cardiomyopathy
  • Kidney failure
  • Pancreatitis
PCCA
PCCB 		Propionic acidemia AR
  • Metabolic acidosis
  • Hyperammonemia
  • 3-hydroxy-propionic acid & 2-methylcitrate in urine
  • Propionylcarnitine on acylcarnitine analysis 1, 3
ARG1 Arginase deficiency AR
  • Hyperammonemia
  • ↑ arginine in plasma
  • ↑ liver enzymes 1, 4
  • Altered level of consciousness
  • Encephalopathy
  • Seizures
  • Vomiting
  • Cognitive impairment
  • Hepatomegaly
ASL Argininosuccinate lyase deficiency AR
  • Hyperammonemia
  • Argininosuccinic acid in plasma or urine
  • ↑ liver enzymes 1, 4
ASS1 Citrullinemia type I AR
  • Hyperammonemia
  • ↑ citrulline in plasma
  • ↑ liver enzymes 1, 4
CPS1 Carbamoylphosphate synthetase I deficiency (See Urea Cycle Disorders Overview.)AR
  • Hyperammonemia
  • Low citrulline in plasma
  • Normal/low orotic acid in urine
  • ↑ liver enzymes 1, 4
OTC Ornithine transcarbamylase deficiency XL
  • Hyperammonemia
  • Low citrulline in plasma
  • ↑ orotic acid in urine
  • ↑ liver enzymes 1, 4
NAGS N-acetylglutamate synthase deficiency (See Urea Cycle Disorders Overview.)AR
  • Hyperammonemia
  • Low citrulline in plasma
  • Normal/low orotic acid in urine
  • ↑ liver enzymes 1, 4
SLC25A13 Citrin deficiency AR
  • Hyperammonemia
  • ↑ citrulline, arginine, methionine, threonine, tyrosine, & lysine in plasma
  • ↑ liver enzymes 1, 4
SLC25A15 Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome AR
  • Hyperammonemia
  • ↑ homocitrulline in urine
  • ↑ liver enzymes 1, 4

From: Classic Isovaleric Acidemia

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.