Toggle Main Menu Toggle Search

Open Access padlockePrints

Further delineation of the phenotypic spectrum of ISCA2 defect: A report of ten new cases

Lookup NU author(s): Professor Robert Taylor


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


© 2017 European Paediatric Neurology Society. Iron-Sulfur Cluster (ISC) biogenesis is a vital cellular process required to produce various ISC-containing proteins. These ISC proteins are responsible for essential functions such as glycine cleavage and the formation of lipoic acid, an essential cofactor of respiratory chain complexes. Defects in ISC biogenesis lead to multiple mitochondrial dysfunction syndromes including: ISCA2 with infantile onset leukodystrophy. Recently, a founder mutation, c.229G > A, p.Gly77Ser in ISCA2 was reported to cause Multiple Mitochondrial Dysfunction Syndrome type 4.In a retrospective review of children diagnosed with the ISCA2 defect, we were able to identify ten new patients who were not reported previously with the identical founder mutation. High CSF glycine levels and elevated glycine peaks on MR spectroscopy were demonstrated in all tested probands. All patients were between 3 and 7 months of age with a triad of neurodevelopmental regression, nystagmus and optic atrophy and leukodystrophy. MRI findings were typical in the patients with diffuse, abnormal white matter signal in the cerebrum, cerebellum, brain stem and spinal cord. The patients ended up in a vegetative state, and often premature death due to respiratory infections.We alert clinicians to consider the ISCA2 defect as a differential diagnosis of infantile onset leukodystrophies affecting the brain as well as the spinal cord, especially in the presence of elevated CSF glycine or elevated glycine peaks in MR spectroscopy.

Publication metadata

Author(s): Alfadhel M, Nashabat M, Alrifai MT, Alshaalan H, Al Mutairi F, Al-Shahrani SA, Plecko B, Almass R, Alsagob M, Almutairi FB, Al-Rumayyan A, Al-Twaijri W, Al-Owain M, Taylor RW, Kaya N

Publication type: Article

Publication status: Published

Journal: European Journal of Paediatric Neurology

Year: 2018

Volume: 22

Issue: 1

Pages: 46-55

Print publication date: 01/01/2018

Online publication date: 16/10/2017

Acceptance date: 06/10/2017

ISSN (print): 1090-3798

ISSN (electronic): 1532-2130

Publisher: W.B. Saunders Ltd


DOI: 10.1016/j.ejpn.2017.10.003


Altmetrics provided by Altmetric