Title:Dihydropteridine Reductase Deficiency - A Rare and Potentially Treatable Cause Mimicking Cerebral Palsy
Volume: 24
Issue: 16
Author(s): Marta Ribeiro*, Mafalda Rebelo, Andreia Pereira, Diana Antunes, Ana Cristina Ferreira and Sandra Jacinto
Affiliation:
- Unidade de Neuropediatria, Área de Pediatria, Centro Hospitalar Universitário de Lisboa Central
Keywords:
Hyperphenylalaninemia, Dihydropteridine reductase deficiency, Cerebral Palsy, Metabolic Screening, Dystonia, QPDR gene
Abstract: Introduction: Dihydropteridine reductase deficiency (DHPRD) is a rare genetic disorder of tetrahydrobiopterin (BH4) regeneration, a cofactor for several enzymes, including phenylalanine hydroxylase. Due to hyperphenylalaninemia (HPA), patients can be detected by the
newborn metabolic screening, when available. The most common symptoms of DHPRD may
mimic cerebral palsy: developmental/cognitive impairment, hypotonia, peripheral hypertonia,
dystonia, feeding difficulties, epilepsy, and microcephaly. The long-term neurodevelopmental
outcome is strongly influenced by the early initiation of effective treatment.
Case Report: A 2-year-old boy, born in Guinea, was evaluated in our center with the diagnosis
of “cerebral palsy”. He was born after a prolonged labor, and had feeding difficulties and severe
developmental delay. Examination revealed microcephaly, axial hypotonia, and dyskinetic
movements without hypertension. No seizures or oculogyric crisis were reported. Brain MRI
showed slight brain atrophy and hyperintensity T2/FLAIR in basal ganglia. The diagnosis of
cerebral palsy was questioned, and further investigation was carried out. HPA raised the possibility of BH4 deficiency, supported by increased biopterin in urine, decreased neurotransmitters
in CSF, and low DHPR enzyme activity. A variant (128_130del (p.(Val43del)) in apparent homozygosity was later detected in the QPDR gene. At 4 years old, he started L-dopa/carbidopa,
oxitriptan, and a phenylalanine-restrictive diet with moderate clinical improvement.
Conclusion: When the diagnosis of “cerebral palsy” is questionable, other etiologies should be
investigated, particularly disorders that have specific disease-modifying treatment. In our patient, the atypical constellation of neurological signs, brain MRI findings, and the nonexistence
of newborn metabolic screening in the country of origin supported additional investigation. The
presence of HPA-associated dystonia was crucial to the investigation and was later confirmed as
DHPRD. Unfortunately, at this stage, the reversibility of the neurological damage in response to
treatment is doubtful
