Mutations of GEMIN5 are associated with coenzyme Q10 deficiency: long-term follow-up after treatment.

GEMIN5 exerts key biological functions regulating pre-mRNAs intron removal to generate mature mRNAs. A series of patients were reported harboring mutations in GEMIN5. No treatments are currently available for this disease. We treated two of these patients with oral Coenzyme Q10 (CoQ10), which resulted in neurological improvements, although MRI abnormalities remained. Whole Exome Sequencing demonstrated compound heterozygosity at the GEMIN5 gene in both cases: Case one: p.Lys742* and p.Arg1016Cys; Case two: p.Arg1016Cys and p.Ser411Hisfs*6. Functional studies in fibroblasts revealed a decrease in CoQ10 biosynthesis compared to controls. Supplementation with exogenous CoQ10 restored it to control intracellular CoQ10 levels. Mitochondrial function was compromised, as indicated by the decrease in oxygen consumption, restored by CoQ10 supplementation. Transcriptomic analysis of GEMIN5 patients compared with controls showed general repression of genes involved in CoQ10 biosynthesis. In the rigor mortis defective flies, CoQ10 levels were decreased, and CoQ10 supplementation led to an improvement in the adult climbing assay performance, a reduction in the number of motionless flies, and partial restoration of survival. Overall, we report the association between GEMIN5 dysfunction and CoQ10 deficiency for the first time. This association opens the possibility of oral CoQ10 therapy, which is safe and has no observed side effects after long-term therapy.

Untangling adaptive functioning of PMM2-CDG across age and its impact on parental stress: a cross-sectional study.

Phosphomannomutase deficiency (PMM2-CDG) leads to cerebellar atrophy with ataxia, dysmetria, and intellectual deficits. Despite advances in therapy, the cognitive and adaptive profile remains unknown. Our study explores the adaptive profile of 37 PMM2-CDG patients, examining its association with parental stress and medical characteristics. Assessment tools included ICARS for the cerebellar syndrome and NPCRS for global disease severity. Behavioral and adaptive evaluation consisted of the Vineland Adaptive Behavior Scale and the Health of the Nation Outcome Scales. Psychopathological screening involved the Child Behavior Checklist and the Symptom Check-List-90-R. Parental stress was evaluated using Parental Stress Index. Results were correlated with clinical features. No significant age or sex differences were found. 'Daily living skills' were notably affected. Patients severely affected exhibited lower adaptive skill values, as did those with lipodystrophy and inverted nipples. Greater severity in motor cerebellar syndrome, behavioral disturbances and the presence of comorbidities such as hyperactivity, autistic features and moderate-to-severe intellectual disability correlated with greater parental stress. Our study found no decline in adaptive abilities. We provide tools to assess adaptive deficits in PMM2-CDG patients, emphasizing the importance of addressing communication, daily living skills, and autonomy, and their impact on parental stress in clinical monitoring and future therapies.

Hypocalcemia: una causa poco frecuente y potencialmente reversible de miocardipatía dilatada / Hypocalcaemia: an unusual and potentially reversible cause of dilated cardiomyopathy

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