Rare neurological disorder found to mimic cerebral palsy
MedWire News: Sepiapterin reductase deficiency (SRD) should be considered in patients with unexplained or atypical cerebral palsy, say researchers.
Their study, published in the Annals of Neurology, shows that the clinical, biochemical, and molecular characteristics of the disorder are non-specific and mimic those of cerebral palsy with hypotonia or dystonia.
SRD is caused by mutation in the SPR gene and is an autosomal recessive disorder that is under-recognized, but treatable. "Individuals with SRD display a [levodopa]-responsive, diurnally fluctuating motor disorder, in most cases associated with cognitive delays and severe neurologic dysfunction," explain study authors Jennifer Friedman (University of California, San Diego, California, USA) and colleagues.
The researchers identified 43 SRD patients, of whom 38 had survey data available. Severity of symptoms varied widely among these 38 patients: some had disabling motor and cognitive deficits whereas others were only diagnosed because a family member was identified with SRD.
The features common to over 65% of SRD patients, and therefore identified as SRD features, included motor and speech delay, axial hypotonia, dystonia, weakness and oculogyric crises with diurnal fluctuation and sleep benefit.
Frequent features, present in 45-65% of patients, included dysarthria, parkinsonian features, hyper-reflexia, psychiatric and/or behavioral abnormalities, sleep disurbance, mental retardation, autonomic signs, and limb hypertonia.
Cerebrospinal fluid analysis was conducted in 29 of the 43 patients. All samples showed low 5-hydroxyindoleacetic acid and homovanillic acid levels, elevated total bipterin, dihydrobiopterin, and sepiapterin levels.
Therapy is aimed at correcting these neurotransmitter and pterin abnormalities and, in this study, 36 patients were treated with levodopa (L-dopa) combined with a peripheral decarboxylase inhibitor. All patients showed significant improvement on receiving this treatment, with three individuals' symptoms being completely resolved. The most effective dose of L-dopa was found to be 3.9 mg/kg/day.
Despite therapeutic success, SRD still poses a diagnostic challenge say Friedman and team. "In infancy, common features of SRD, hypotonia and developmental delays, are non-specific and mimic other neurologic conditions including, as in this series, CP [cerebral palsy]," they write.
The researchers add that clinicians should remain vigilant to avoid mis- or delayed diagnosis, as inadequate treatment could lead to "irreversible neurologic dysfunction."
They recommend physicians consider SRD or other neurotransmitter disorder "in all patients with a dopa-responsive motor disorder, patients with developmental delays and axial hypotonia, and in patients with unexplained or atypical 'cerebal palsy' especially if hypotonia or dystonia are present."
By Chloe McIvor