Rick and Cristy Spooner lived for more than a decade with a devastating mystery. What was the rare genetic disease afflicting their daughter Calyn? As a baby Calyn suffered violent seizures, but neurologists didn’t know why. Unable to walk without the help of a walker, Calyn has grown up with significant motor, cognitive and emotional impairment. The Spooners could never get a diagnosis, except than an MRI showed a strange pattern on her cerebellum that doctors had never seen before.
When the couple’s third daughter, Ryann, began to exhibit similar symptoms shortly after her birth in 2009, it was a terrible deja vu.
Finally, 14 years after Calyn’s birth, advances in genetic testing gave the Spooners some answers. A new test called “exome sequencing” showed that Calyn and Ryann had inherited mutations from both parents on a gene known as NUBPL. That caused a defect in an important enzyme called complex I, which prevents their mitochondria — the powerhouses inside the body’s cells — from producing the energy their cells need to work properly.
Today, there is no specific drug for Mitochondrial Complex I Deficiency, the rare disease that affects Calyn and Ryann. Doctors treat the Spooner girls with a “cocktail” of vitamins and enzymes used as therapy for other mitochondrial diseases. It’s a treatment that has improved their daily lives, but is still far from a cure.
Rick and Cristy Spooner shared their story of a search for a diagnosis in a heart-felt documentary, “The life we live.” Since going public with their journey, they have become tireless advocates for medical research to unlock the mysteries of the NUBPL gene, which has implications not just for Complex I Deficiency but for Parkinson’s Disease as well.
Rick and Cristy Spooner are true partners, in marriage and life. Married in 1998, this dynamic couple built a successful loan company, Loan-Closers.com. At home, they have faced greater challenges – and forged greater meaning in their lives – through raising three daughters, two with a rare and physically debilitating disease. They founded the Spooner Girls Foundation to advocate for more medical research into Complex I Deficiency, in hopes of improving the lives of their daughters and others like them.
Calyn Spooner, born in 1998 is a lot like a typical teenage girl. Known in the family as “Cali” or “Cali Bear,” Calyn is a social butterfly who loves her friends, enjoys face-timing with her friends, listening to music, and dancing. Loved by everyone who meets her, Calyn is known for her beautiful, sweet smile, which never fails to light up a room.
Raelyn Spooner, born in 2006, is the writer in the family. A book smart girl, she loves to compose quirky stories, and dreams of creating her own YouTube show. She is also an athlete who swims and plays All-Star softball. As the healthy sister of two girls with Complex I Deficiency, Raelyn has developed a sense of compassion and maturity beyond her young age. As her mom says, “This is a sweet girl and a big helper with a huge heart.”
Ryann, born in 2009, is known in the family as “Pistol.” This little girl is constantly on the go. After she learned to walk without a walker at four years old, her parents have been scrambling to keep up with her ever since. Independent and determined, Ryann is making great strides academically, learning colors, shapes and sight words.
Virginia Kimonis1,2, Kelly Gonzalez3, Wenqi Zeng3, Phillip Gray3, Sha Tang3, Jennifer Wei3, Xiang Li3, Hsiao-Mei Lu3, Hong Lu3, Anton N. Hasso4, Mateusz Wydro5, Andrew Maclean5, Janneke Balk5, and Elizabeth Chao1,3.
1Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine
2Childrens Hospital of Orange County, Orange, CA
3Ambry Genetics, Aliso Viejo, CA
4Radiological Sciences, School of Medicine, University of California, Irvine, California, USA
5John Innes Centre, Colney Lane, Norwich, UK
Exome sequencing was performed on a 14 year-old female and her 3 year-old sister with nystagmus, ataxia, global developmental delays, hyperreflexia, clonus and MRI findings of cerebellar and pons hypoplasia. The family history was remarkable for tremor in several relatives. There was no consanguinity. Nearly a decade of molecular, cytogenetic, and biochemical testing was uninformative in the girls. Exome sequencing revealed compound heterozygous alterations of the NUBPL gene (c.311T>C; p.L104P and c.815-27T>C), a Complex I assembly factor. The c.311T>C missense alteration is located at a highly conserved amino acid. The previously reported c.815-27T>C alteration is located at a highly conserved nucleotide and previous in vitro analyses demonstrated splicing defects. The NUBPL gene was first reported in association with mitochondrial Complex I deficiency syndrome (CI deficiency, MIM_252010) in 2010. Only seven families have been reported worldwide, which displayed clinical overlap with the two siblings in this family (eighth family). Each mutation individually renders the yeast homologue of NUBPL entirely non-functional. iPS studies are also in progress.
After nearly a decade of unsuccessful analyses, diagnostic exome sequencing led to a diagnosis for the family. Yeast studies have led to novel therapies in the siblings. We are interested in studying new patients with NUBPL disease.
The more we connect with other NUBPL families, the closer we get to finding a cure. Do you have NUBPL or do you think you may? Or, are you a researcher who is interested in studying NUBPL? Please contact us. We want to hear from you. Although some families are public about their journey, we respect your desire for privacy.