Objective: To report the outcome of a 6.3-year-old girl with SRD diagnosed and treated since the fifth month of life.

Background: Sepiapterin reductase deficiency (SRD) is a rare disorder of tetrahydrobiopterin biosynthesis resulting in impaired production of monoamine neurotransmitters (NTs). The majority of the patients presents in infancy or childhood with developmental delay, axial hypotonia, dystonia, weakness, oculogyric crises, and diurnal fluctuation of symptoms. While movement disorders improve under low-dose L-dopa and 5-OH-tryptophan, neurocognitive outcome is unfavourable in almost all the reported patients.

Method: Case report.

Results: This girl was born from nonconsanguineous parents after a normal pregnancy and delivery. During the first days of life she presented upper limb jerks that became generalized and continuous. Later on, oculogyric crises were noticed. At 5 months she exhibited severe motor delay, a spasmodic pattern of extensor stiffening of the head and trunk, hypokinesia, limb rigidity, and almost continuous oscillatory movements of the limbs, trunk, and head at rest. CSF analysis of NTs metabolites showed low levels of homovanillic acid, 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol, and increased levels of sepiapterin. Molecular analysis of SPRgene revealed p.Arg150Gly (c.448A>G) and p.Lys251* (c.751A>T) pathogenic variations. Treatment with increasing doses of L-dopa/carbidopa and 5-OH-tryptophan was started and resulted in a prompt improvement of movement disorders and achievements of motor milestones. At 12 months CSF analysis detected normal NTs levels. At 16 months of age she was able to walk without support; dystonic postures of the upper limbs and gait abnormalities with impaired postural control were observed until the age of 24 months when selegiline was introduced. Language development was mild delayed due to an oral dyspraxia. She now attends primary school with a normal social and cognitive development with only a minor impairment in sustained attention and fine motor coordination.

Conclusion: There are no outcome studies in early-treated SRD patients so far. We confirm the dramatic efficacy of low dosage of biogenic amine precursors on movement disorders in this disease, but also the potential effectiveness of a very early treatment in promoting a normal neurocognitive and neuromotor development.

References: Leuzzi V, Carducci C, Tolve M, Giannini MT, Angeloni A, Carducci C. Very early pattern of movement disorders in sepiapterin reductase deficiency. Neurology. 2013 Dec 10;81(24):2141-2. Friedman J, Roze E, Abdenur JE, Chang R, Gasperini S, Saletti V, Wali GM, Eiroa H, Neville B, Felice A, Parascandalo R, Zafeiriou DI, Arrabal-Fernandez L, Dill P, Eichler FS, Echenne B, Gutierrez-Solana LG, Hoffmann GF, Hyland K, Kusmierska K, Tijssen MA, Lutz T, Mazzuca M, Penzien J, Poll-The BT, Sykut-Cegielska J, Szymanska K, Thöny B, Blau N. Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. Ann Neurol. 2012 Apr;71(4):520-30.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-outcome-in-early-treated-sepiapterine-reductase-deficiency-srd-a-case-report/