Combined Sepiapterin Reductase and Methylmalonyl-CoA Epimerase Deficiency in a Second Patient: Cerebrospinal Fluid Polyunsaturated Fatty Acid Level and Follow-Up Under L-DOPA, 5-HTP and BH4 Trials

JIMD Reports
Michel MazzucaPascale de Lonlay

Abstract

Objective/context: We describe the second patient presenting the combination of two homoallelic homozygous nonsense mutations in two genes distant from 1.8 Mb in the chromosome 2p13-3, the methylmalonyl-CoA epimerase gene (MCEE) and the sepiapterin reductase gene (SPR). The patient was born from consanguineous parents. He has presented a moderate but constant methylmalonic acid (MMA) excretion in urine associated with a mental retardation. The first homozygous mutation was identified in the MCEE gene (c.139C>T; p.Arg47*). Progressive dystonia and cataplexy narcolepsy led to diagnose the second homozygous mutation in the SPR gene: c.751A>T; p.Lys251*. Sepiapterin reductase deficiency (SRD) was characterized by a defect in tetrahydrobiopterin (BH4), the cofactor of several hydroxylases needed for the synthesis of neurotransmitters. A treatment with L-DOPA/carbidopa and 5-HTP dramatically improved the dystonic posture, the mood and the hypersomnia, proving that the pathogenesis was due to SRD. A supplementation with BH4 did not induce additional clinical benefit, although HVA and HIAA increased in CSF. The polyunsaturated fatty acids were measured in CSF as the markers of the neuronal stress. We have shown that DHA and its precurs...Continue Reading

Citations

Nov 7, 2017·International Journal of Molecular Sciences·Lenaig Abily-DonvalAbdellah Tebani
Sep 20, 2017·Journal of Inherited Metabolic Disease·Alice KusterUNKNOWN Individual contributors who contributed to this work
Aug 1, 2020·Journal of Cellular and Molecular Medicine·Yao WuMeixiao Zhan
May 28, 2020·Orphanet Journal of Rare Diseases·Thomas OpladenUNKNOWN International Working Group on Neurotransmitter related Disorders (iNTD)
Apr 14, 2016·Neuroscience and Biobehavioral Reviews·M SmitM A Tijssen
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alisa PautovaAlexander Revelsky

❮ Previous
Next ❯

Related Concepts

Related Feeds

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.