5. Case Study 4

In 1995 a female infant, the first child of consanguineous parents, developed a severe encephalopathy associated with hyperammonaemia and died within the first week of life. No other investigations were available before death but a skin biopsy was taken. An assay for argininosuccinate lyase showed no activity.

The couple declined prenatal diagnosis for subsequent pregnancies. A second child was treated prospectively from birth with IV sodium benzoate and arginine. The results of monitoring in the first week of life showed no significant increase in blood ammonia and a no argininosuccinate in blood or urine.

A third child born in 1999 was managed similarly.

 

The results of initial blood investigations were as follows:

 

References 28 to 31 will enable you to understand and learn from this case.

Comment: Although the ammonia and glutamine level are normal, ASA is raised, confirming that this infant is affected; hyperammonaemia is generally easy to prevent.

Following confirmation of the diagnosis of ASA, the child was continued on oral medication and a protein restricted diet. He remained well and had no episodes of hyperammonaemic encephalopathy. By 9 months he was crawling. A formal DQ at 13 months gave scores of 84-110. At 13 months he was noted to have a firm hepatomegaly and raised liver transaminases. At 2 years there was evidence of global developmental delay but with marked speech delay. By 4 he was only using single words. At 6 years he had a tonic–clonic convulsion. An EEG showed diffuse slow wave activity with a right temporal and occipital abnormality. An MR brain scan was normal. He had further fits and was started on treatment with carbamazepine.

Unfortunately, this is not that unusual for the severe neonatal onset type. Reference 20 will help you understand this.

Learning objectives from this case report:

  1. To know how the diagnosis of argininosuccinate lyase can be made.
  2. To know the long term outcome for argininosuccinate lyase deficiency even when neonatal hyperammonaemia can be avoided.