Arginase Deficiency in an Immigrant Patient Without Medical Care

Introduction: Arginase deficiency is an inborn error of metabolism affecting the last step of the urea cycle. Screening for arginase deficiency is included on most newborn screening in the United States. However, some patients have normal arginine levels during infancy and become symptomatic only when arginine and ammonia levels accumulate later in childhood. Without treatment, the disease progression can include developmental regression, growth limitation, diffuse spasticity, and epilepsy.

Case Description: A 24 year-old woman was brought to the pediatric emergency department by her mother for convulsions. The patient recently moved from Honduras where she was in the care of her grandmother. She was developmentally normal until four years-old, when she developed seizures and subsequently lost the ability to speak or move her limbs. Her cognitive development was around 12 years of age. Additional medical history was unknown. Physical exam in the ED was notable for cachexia, bilateral upper and lower extremity spasticity with contractures, initial seizure activity evidenced by repeated mouth movements, and minimal responsiveness. Laboratory evaluation included lactic acid of 3.2 mmol/L, creatinine kinase of 4,999 U/L, aspartate aminotransferase (AST) 130 U/L, alanine aminotransferase (ALT) 149 U/L and normal BUN and creatinine. Seizures stopped with lorazepam and levetiracetam, and she was admitted for further monitoring. On hospital day two, she was noted to have new anisocoria. CT head showed age-advanced diffuse parenchymal loss of unknown etiology. MRI brain did not show a distinct epileptogenic focus. Additional labs showed an ammonia of 319 µmol/L, arginine of 784 µmol/L (ref 15-128) and ornithine of 28 µmol/L (ref 48-196), a pattern consistent with arginase deficiency. She began therapy with a vegan diet, sodium benzoate and levocarnitine with normalization of serum ammonia levels and decrease in arginine levels. The patient could not afford targeted treatment for urea cycle disorders, glycerol phenylbutyrate.

Discussion: This case describes the complications of untreated congenital metabolic disorders. Early diagnosis and treatment are the cornerstones of management to prevent developmental and neurological effects of congenital metabolic disease. However, in areas where testing for inborn errors of metabolism is not a part of routine newborn screening or where screening cutoffs are too high, patients are at risk of unrecognized disease during childhood. Aspects of the patient’s case that make metabolic disease more likely are childhood onset, seizures without a distinct intracranial focus, and loss of developmental milestones.

Conclusion: Progression of arginase deficiency and similar conditions can be prevented with early diagnosis and initiation of therapy. Preparing physicians to recognize potential disorders in metabolism can be lifesaving for patients of all ages.