In this study, in all patients with a definite diagnosis of PDS according to the criteria published by Baxter,8
α‐AASA dehydrogenase deficiency could be proven at the metabolite level by demonstrating elevated concentrations of α‐AASA (plasma and urine) and PA (plasma). The diagnosis was also confirmed in two out of three patients with probable PDS and in three out of four patients with possible PDS.
The diagnosis of probable PDS could not be confirmed in one patient (patient 6). She is a younger sister of a girl with a definite clinical diagnosis of PDS and a metabolically confirmed diagnosis of α‐AASA dehydrogenase deficiency (patient 4). She had subtle neonatal seizures with only minimal epileptic discharges on a 24‐h EEG, which responded to 100 mg of pyridoxine given intravenously. She is performing well at school. Her normal development makes a diagnosis of PDS unlikely since most PDS patients suffer from, at least a mild, encephalopathy with learning difficulties.5
However, the nature of the neonatal seizure‐like period remains unexplained. We advised a trial period of pyridoxine withdrawal but could not convince the parents to stop treatment. DNA analysis of patients included in our study are pending.
In patient 11, originally diagnosed with possible PDS, pyridoxine was recently withdrawn without recurrence of seizures. We consider PDS a very unlikely diagnosis in this patient because of the above observation and the fact that the child is developing well. The parents did not want to cooperate with further metabolic investigations.
In our first report,6
we described two patients (patients 12 and 13 in that paper) who did not meet the criteria for definite, probable or possible PDS. In both patients we have now demonstrated normal α‐AASA concentrations in plasma and urine, as would be expected (data not shown).
This report is the first nationwide population‐based study on metabolically confirmed PDS. Our results show that at least 10 children with PDS were born in the Netherlands between January 1991 and December 2004. As 2
697 children were born in the Netherlands during this time (adapted from http://statline.cbs.nl
), the birth incidence of biochemically proven PDS in the Netherlands is at least 1: 276
000 children. This study further shows that most patients, namely nine out of 11 (82%), were diagnosed correctly using the criteria proposed by Baxter. Thus, in circumstances where metabolic examination of α‐AASA and/or PA is not possible, applying the clinical criteria proposed by Baxter seems a reliable method to establish a diagnosis of PDS.
The concentrations of α‐AASA and PA, in urine as well as in plasma, vary considerably in patients with PDS. A remarkably wide range of α‐AASA and PA levels in patients has also been found by Mills et al
in their first report on α‐AASA dehydrogenase deficiency in PDS.5
We have no clear explanation for this wide range. Hypothetically it might reflect different levels of α‐AASA dehydrogenase residual activity, dietary protein (L‐lysine) intake, or the amount of supplemental pyridoxine. It is tempting to speculate that optimum treatment (ie, pyridoxine dosage) in PDS might be achieved by focusing on the concentrations of α‐AASA and PA.