Dihydropteridine reductase deficiency: The first Moroccan case report

Abstract

Background

DHPRD (dihydropteridine reductase deficiency) is a very rare disorder that causes hyperphenylalaninemia (HPA), characterized by an accumulation of phenylalanine (Phe) and a profound deficit in the neurotransmitters dopamine and serotonin in the central nervous system with an alteration in folate status. It is an autosomal recessively inherited disorder caused by genetic changes in the QDPR gene.

Case presentation

A Moroccan 3-year-old girl, from a consanguineous marriage with a history of death and neurological illness in the siblings. The proband presents a very severe clinical picture; profound psychomotor delay with hypotonia, epileptic encephalopathy, abnormal movements and dysautonomia signs. The diagnosis of DHPRD was confirmed by DHPR activity assay and genetic testing. The patient was placed on a Phe-restricted diet and given augmented neurotransmitter therapy, which included levo-dopa/carbidopa, and 5-hydroxytryptophan with folinic acid. The improvement under treatment was not spectacular which is most likely due to the delay in diagnosis and management.

Discussion/conclusion

Significant advancements have been achieved in comprehending the physiopathology, the screening procedures, diagnostic techniques, treatment options, and molecular genetics pertaining to DHPRD. However, in countries where neonatal screening for phenylketonuria (PKU) is not established, severe forms of DHPRD with irreversible sequelae continue to be diagnosed. The long-term neurodevelopmental outcomes of patients with DHPRD are strongly influenced by early initiation of effective treatment; therefore, screening for PKU must be systematic and therapy should not be delayed.