Our mission of the NUBPL Foundation is to raise awareness and fund research towards the development of life-saving treatments and a cure for NUBPL, a mitochondrial complex 1 deficiency disorder.
NUBPL is a progressive neurodegenerative disease with zero FDA approved treatments. Patients present clinical symptoms between the ages of 3-24 months, including onset neurological symptoms: cerebellar dysfunction – progressive cerebellar & pons hypoplasia, global developmental delay, inability to walk, ataxia, nystagmus, and speech articulation difficulty.
Researchers are studying NUBPL with the purpose and hope of delivering a treatment breakthrough for patients. Research dollars are difficult to come by for rare diseases. Every dollar donated keeps hope alive for the future. Help us turn hope into action today.
What is NUBPL?
Iron-sulfur protein NUBPL (IND1) also known as nucleotide-binding protein-like (NUBPL) is an iron-sulfur (Fe/S) protein that, in humans, is encoded by the NUBPL gene, located on chromosome 14q12. Mutations in the NUBPL gene may cause a rare form of mitochondrial complex I disorder.
Clinical Features
Age of onset: 1-2 years old
Developmental delay: Some patients
Delay: Motor; Unable to walk
Speech: Abnormal (Dysarthria)
Eyes: Strabismus; Nystagmus
Ataxia: Trunk & Limbs
Contractures
Spasticity
Cognitive: Normal or Reduced
Myopathy
Other organs: Normal
Course: Progressive, continuous or episodic
Laboratory Signs
MRI: Leukoencephalopathy with abnormal:
– Cerebellar cortex: Progressive
– Cerebral white matter, deep: May resolve
– Corpus callosum: May resolve
*Please note that although these are characteristic MRI findings, there are others including abnormalities in the grey matter of the cerebellum, as discussed in the blog, Hope for Katherine Belle.
Lactate: Serum normal or high; CSF normal or high
NUBPL protein: Reduced
Muscle biopsy
– Histology: Ragged red fibers; No COX- fibers
– Biochemistry: Complex I deficiency
Research
Balk, J. “Discovery of the NUBPL gene and its role in Complex 1 assembly.”
Kevelam, S. “NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern.” Neurology 80 (17): 1577–1583.
P.S. Eis, E. Hatchwell, J.W. Langston, B. Schüle. Genetic Variations in Mitochondrial Complex I Genes Are Associated with Parkinson’s Disease. Keystone Symposium: Parkinson’s Disease: Genetics, Mechanisms and Therapeutics, Keystone CO, March 2014.
P.S. Eis, B. Schüle, S. Kim, J.W. Langston, V.E. Kimonis, E. Hatchwell. NUBPL mutations link Parkinson’s disease and other movement disorders to recessive Complex I deficiency. Abstract/Program #1403. Presented at the 66th Annual Meeting of The American Society of Human Genetics, October 2016, Vancouver, Canada.
V. Kimonis, P.S. Eis, S. Parikh, D. Scott, M.K. Koenig, A. Maclean, S. Tang, A.N. Hasso, M. Wydro, J. Balk, E. Chao, E. Hatchwell. Mitochondrial studies in a novel disorder associated with NUBPL associated mitochondrial complex I deficiency in patients with global developmental delays, ataxia, cerebellar and pons hypoplasia. Abstract/Program #2519. Presented at 66th Annual Meeting of The American Society of Human Genetics, October 2016, Vancouver, Canada.
Sheftel, A. “Human Ind1, an Iron-Sulfur Cluster Assembly Factor for Respiratory Complex I”. Mcb.asm.org. Retrieved 25 April 2015
Sheftel, A. “Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I”. Mol. Cell. Biol. 29 (22): 6059–6073. PMID 19752196.