Abstract
Dopa-responsive dystonia due to sepiapterin reductase deficiency (OMIM#612716) is caused by recessive mutations in the gene encoding sepiapterin reductase (SPR), which plays an important role in the biosynthesis of tetrahydrobiopterin (BH4). One Jordanian patient to first cousin parents is reported in this study. The parents of the proband have recognized the symptoms of their daughter at six months old with motor developmental delay. The symptoms were progressed after-then to include speech delay, seizure, ataxia, oculomotor apraxia, dysarthia and choreoathetosis. Despite of these symptoms, the clinicians in Jordan were unable to diagnose the case. In August 2018, the proband (8 years old) was presented to the department of biotechnology and genetic engineering at Philadelphia University in Jordan for the purposes of performing whole exome sequencing (WES). Analysis of WES data has revealed novel homozygous frameshift variant in the gene SPR (NM_003124.4:c.40delG,p.Ala15Profs*100). The variant is heterozygous in the parents and in the healthy male siblings. Therefore, the studied case was diagnosed with sepiapterin reductase deficiency. Because this disease is likely to be treated recommendations were given to the family immediately to start treatments trials. The case in this study illustrates the difficulties of diagnosing sepiapterin reductase deficiency based on clinical symptoms only and thus renders the possibilities of early management. Also, this study reinforces the importance of running WES to undiagnosed neurodevelopmental cases.
Highlights
sepiapterin reductase (SPR) is required for the biosynthesis of tetrahydrobiopterin (BH4) which on its turn required for the biosynthesis of serotonin and catecholamine.[1]
Ethical Approval: This study was approved by the deanship of scientific research and graduate studies at Philadelphia University/Amman-Jordan and informed consents were obtained from all family members
Dopa-responsive dystonia report mentions abnormal study case in the wrist and ankle, (2) brain MRI and the conclusion was unremarkable, (3) routine 24 channels digital EEG record which showed moderate to high voltage theta activity, (4) blood biochemistry which states high lactic acid (3.5 mmol/L, reference is 0.52.2 mmol/L), high asparagine (104 micromol/L, reference 23-79 micromol/L), low creatinine (30 micromol/L, reference 53-123 micromol/L)
Summary
1. Tawfiq Froukh, Department of Biotechnology and Genetic Engineering, Philadelphia University, Jerash Road, Amman (19392) Jordan. Dopa-responsive, due to sepiapterin reductase deficiency (OMIM#612716) is a rare inherited neurotransmitter disorder caused by autosomal recessive mutations in the gene sepiapterin reductase (SPR). SPR is required for the biosynthesis of tetrahydrobiopterin (BH4) which on its turn required for the biosynthesis of serotonin and catecholamine.[1]. This rare disease is underdiagnosed despite the clinical hallmarks of paroxysmal stiffening, oculogyric crises, hypotonia in early stages, cognitive symptoms, speech disturbances, motor delay and dystonic movements in later stages.[2,3] In this study, new mutation in the SPR gene using
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