Dihydropteridine Reductase Deficiency - A Rare and Potentially Treatable Cause Mimicking Cerebral Palsy

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

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

Cite this article as:

Ribeiro Marta*, Rebelo Mafalda, Pereira Andreia, Antunes Diana, Ferreira Cristina Ana and Jacinto Sandra, Dihydropteridine Reductase Deficiency - A Rare and Potentially Treatable Cause Mimicking Cerebral Palsy, Endocrine, Metabolic & Immune Disorders - Drug Targets 2024; 24 (16) . https://dx.doi.org/10.2174/0118715303279209231026044120

DOI https://dx.doi.org/10.2174/0118715303279209231026044120	Print ISSN 1871-5303
Publisher Name Bentham Science Publisher	Online ISSN 2212-3873