Tuğçe Aksu Uzunhan1, Nafiye Emel Çakar2, Serhat Seyhan3, Kürşad Aydin4. 1. University of Health Sciences, Okmeydanı Training and Research Hospital, Division of Pediatric Neurology, Istanbul, Turkey. Electronic address: tugce.aksuuzunhan@saglik.gov.tr. 2. University of Health Sciences, Okmeydanı Training and Research Hospital, Division of Paediatric Metabolism, Istanbul, Turkey. 3. Medipol University, Department of Medical Genetics, Istanbul, Turkey. 4. Medipol University, Department of Pediatric Neurology, Istanbul, Turkey.
Abstract
BACKGROUND: Genetic defects in the NFU1, an iron-sulfur cluster scaffold protein coding gene, which is vital in the final stage of assembly for iron sulfur proteins, have been defined as multiple mitochondrial dysfunctions syndrome I. This disorder is a severe autosomal recessive disease with onset in early infancy. It is characterized by disruption of the energy metabolism, resulting in weakness, neurological regression, hyperglycinemia, lactic acidosis, and early death. PATIENT DESCRIPTION: This report documents the case of a 27-month-old girl, who showed clinical signs and symptoms of spastic paraparesis with a relapsing-remitting course. The patient had a sister with a severe phenotype who died at the age of 16 months. RESULTS: Magnetic resonance imaging revealed hyperintensity of the cerebral white matter that was more prominent in the frontal regions, with milder involvement in the posterior periventricular regions. There was also evidence of partial cystic degeneration and cavitation in the frontal regions. In addition, she had hyperglycinemia. Homozygous NM_001002755.4:c.565G>A (p.Gly189Arg) mutation was identified in the NFU1 gene; this had not previously been reported as homozygous. CONCLUSION: Hyperglycinemia and cavitating leukodystrophy are suggestive of an NFU1 mutation diagnosis. An intrafamilial phenotypic variation has not been published in NFU1-associated disorders before. Presenting with spasticity as a rare phenotype, NFU1 mutations could be considered a genetic mimic of cerebral palsy.
BACKGROUND: Genetic defects in the NFU1, an iron-sulfur cluster scaffold protein coding gene, which is vital in the final stage of assembly for iron sulfur proteins, have been defined as multiple mitochondrial dysfunctions syndrome I. This disorder is a severe autosomal recessive disease with onset in early infancy. It is characterized by disruption of the energy metabolism, resulting in weakness, neurological regression, hyperglycinemia, lactic acidosis, and early death. PATIENT DESCRIPTION: This report documents the case of a 27-month-old girl, who showed clinical signs and symptoms of spastic paraparesis with a relapsing-remitting course. The patient had a sister with a severe phenotype who died at the age of 16 months. RESULTS: Magnetic resonance imaging revealed hyperintensity of the cerebral white matter that was more prominent in the frontal regions, with milder involvement in the posterior periventricular regions. There was also evidence of partial cystic degeneration and cavitation in the frontal regions. In addition, she had hyperglycinemia. Homozygous NM_001002755.4:c.565G>A (p.Gly189Arg) mutation was identified in the NFU1 gene; this had not previously been reported as homozygous. CONCLUSION: Hyperglycinemia and cavitating leukodystrophy are suggestive of an NFU1 mutation diagnosis. An intrafamilial phenotypic variation has not been published in NFU1-associated disorders before. Presenting with spasticity as a rare phenotype, NFU1 mutations could be considered a genetic mimic of cerebral palsy.
Authors: Peter A Kropp; Jing Wu; Michael Reidy; Sanjay Shrestha; Kyle Rhodehouse; Philippa Rogers; Michael N Sack; Andy Golden Journal: PLoS Genet Date: 2021-08-27 Impact factor: 5.917