title: Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine.
abstract: Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can aid in identifying this condition, although their relationship to the clinical manifestations is not known. Herein we describe clinical and laboratory findings in two fraternal twins with hawkinsinuria who presented with failure to thrive and metabolic acidosis. Close clinical follow-up and laboratory testing revealed previously unrecognized hypoglycemia, hypophosphatemia, combined hyperlipidemia, and anemia, along with the characteristic urinary metabolites, including massive pyroglutamic aciduria. Treatment with N-acetyl-L-cysteine (NAC) restored normal growth and normalized or improved most biochemical parameters. The dramatic response to NAC therapy supports the idea that glutathione depletion plays a key role in the pathogenesis of hawkinsinuria.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA. gomezosp@stanford.edu.
authors.forename: Natalia
authors.identifier: 0000-0002-6740-1154
authors.initials: N
authors.lastname: Gomez-Ospina
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Anna I
authors.initials: AI
authors.lastname: Scott
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Gia J
authors.initials: GJ
authors.lastname: Oh
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Potter
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Veena V
authors.initials: VV
authors.lastname: Goel
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Destino
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Baugh
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Enns
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Niemi
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, H 315, Stanford, CA, 94305-5208, USA.|Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Cowan
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000138:Acidosis / Q000473:pathology; D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005981:Glutathione Synthase / Q000172:deficiency; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D010641:Phenotype; D014427:Twins; D020176:Tyrosinemias / Q000188:drug therapy* / Q000473:pathology
chemical_list: D006899:Mixed Function Oxygenases; D005981:Glutathione Synthase; D000111:Acetylcysteine