A New Form of Prolonged Transient Tyrosinemia Presenting With Severe Metabolic Acidosis

Abstract

Yet another form of tyrosinemia is described, in a young baby who developed metabolic acidosis and ceased to grow when weaned from breast milk onto a higher protein formula. Severe tyrosyluria and mild tyrosinemia cleared on a low-protein diet which also corrected the acidosis. However, restoration of growth required a normal protein intake with very greatly reduced amounts of phenylalanine and tyrosine. The metabolic fault later resolved spontaneously at about 12 months of age. Mental development appears normal and liver disease was never apparent. The patient and her mother both excrete quite large quantities of an unidentified peptide.

Chronic Tyrosinemia Associated with 4-Hydroxyphenylpyruvate Dioxygenase Deficiency with Acute Intermittent Ataxia and without Visceral and Bone Involvement

“…Finally, Danks et ai. (3,22) reported a patient with mild prolonged, transient tyrosinemia who presented with severe metabolic acidosis in whom the unusual tyrosine metabolites, hawkinsin and cis-and trans-4-hydroxycyclohexylacetic acid were found in the urine. It was postulated that these metabolites were derived from an intermediate of the 4HPPD reaction and that the child and her mother were heterozygous for a defect of this enzyme which was able to oxidize and decarboxylate pHPPA but was unable to rearrange the intermediate to homogentisic acid.…”

“…with severe metabolic acidosis who excreted the unusual tyrosine metabolites hawkinsin and cis-and trans-4-hydroxycyclohexylacetic acids in the urine (3,22,26). The' primary abnormality is thought to be in the rearrangement of an intermediate formed in the 4HPPD reaction.…”

Long-term follow up of a new case of hawkinsinuria

“…There was no tyrosylor pyroglutamic aciduria at that time. Screening for urinary amino acids by high voltage electrophoresis yielded an unknown ninhydrin positive spot at a similar position as published for substance x previously [3]. Staining with iodoplatinate showed this to be a sulfurcontaining amino acid.…”

“…The condition is associated with failure to thrive, prolonged tyrosyluria and metabolic acidosis. In analogy to the ®ve symptomatic children with hawkinsinuria described [1,3,4,10] the disease in our patient started after weaning from breast milk at the age of 3 months with recurrent vomiting, inappetence, and failure to thrive. Investigation during several admissions disclosed renal tubular acidosis of unknown reason, prolonged tyrosyluria and 5-oxoprolinuria during acute illness.…”

“…Since the description of the ®rst case [3], only three additional symptomatic patients and several biochemically aected but clinically asymptomatic family members have been detected so far [1,4,10]. We describe here a new case of hawkinsinuria who was ®rst misdiagnosed as having fructose intolerance.…”