No specific curative treatment exists for patients with Complex I deficiency due to NUBPL mutations presenting with cerebellar dysfunction (e.g., ataxia, dysarthria, nystagmus, and tremor), and less commonly with NUBPL-associated Leigh syndrome and cerebellar dysfunction. The lactate level is rarely elevated and does not require any specific treatment.
A cocktail of multivitamins and antioxidants are often used in the hope of improving mitochondrial function. Most commonly these include riboflavin, thiamine, and coenzyme Q10 (at 50-100 mg/day). However, treatment of the Yarrowia lipolytica model for NUBPL disease by the laboratory of Dr. Janneke Balk (unpublished data) showed that none of the compounds rescued the complex I defect in the yeast mutant, although some small improvements were seen under some conditions.
Sodium valproate and barbiturates should be avoided because of their inhibitory effect on the mitochondrial respiratory chain. Anesthesia can potentially aggravate respiratory symptoms and precipitate respiratory failure, so careful consideration should be given to its use and to monitoring of the individual prior to, during, and after anesthetic procedures.
No specific recommendations have been published for NUBPL disease. Nevertheless, the consensus-based recommendations of a panel of members with several different areas of expertise can be considered for optimal care and management for patients with this primary mitochondrial disease. Kimonis et al. (2021) reported treatment in four new patients with compound heterozygous variants in the NUBPL gene. The most striking finding was the milder phenotype in the younger sibling (Patient 1B) who started treatment at a much younger age with a mitochodrial cocktail of coenzyme Q10, riboflavin, vitamin B-complex with vitamins C and E, lipoic acid, and biotin. The two patients in this family (1A and 1B) also received N-acetyl cysteine.