A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation
-
Asburce Olgac
,
Ülkühan Öztoprak
Abstract
Background
Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation.
Case presentation
A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage.
Conclusions
We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Ethical statement: In accordance with the Helsinki Declaration, the participants were informed about the exact procedure of the study and took part voluntarily. All participants gave their approval.
Disclosure of potential conflicts of interest: None declared.
Research involving human participants and/or animals: Not applicable.
Informed consent: Informed consent has been obtained from parents for the preparation of this manuscript.
References
1. Crane FL, Navas P. The diversity of coenzyme Q function. Mol Asp Med 1997;18(Suppl):S1–6.10.1016/S0098-2997(97)00016-2Search in Google Scholar
2. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171–99.10.1016/j.bbamem.2003.11.012Search in Google Scholar PubMed
3. Duncan AJ, Bitner-Glindzicz M, Meunier B, Costello H, Hargreaves IP, et al. A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am J Hum Genet 2009;84:558–66.10.1016/j.ajhg.2009.03.018Search in Google Scholar PubMed PubMed Central
4. Smith A, Ito Y, Ahmed A, Schwartzentruber JA, Beaulieu CL, et al. Family segregating lethal neonatal coenzyme Q10 deficiency caused by mutations in COQ9. J Inherit Metab Dis 2018;41:719–29.10.1007/s10545-017-0122-7Search in Google Scholar PubMed
5. Merriman B, IonTorrent R&D Team, Rothberg JM. Progress in ion torrent semiconductor chip based sequencing. Electrophoresis 2012;33:3397–417.10.1002/elps.201200424Search in Google Scholar PubMed
6. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, et al. Integrative genomics viewer. Nat Biotechnol 2011;29:24–6.10.1038/nbt.1754Search in Google Scholar PubMed PubMed Central
7. Luna-Sánchez M, Díaz-Casado E, Barca E, Tejada MÁ, Montilla-García Á, et al. The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene. EMBO Mol Med 2015;7:670–87.10.15252/emmm.201404632Search in Google Scholar PubMed PubMed Central
8. Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci USA 1989;86:2379–82.10.1073/pnas.86.7.2379Search in Google Scholar PubMed PubMed Central
9. Sobreira C, Hirano M, Shanske S, Keller RK, Haller RG, et al. Mitochondrial encephalomyopathy with coenzyme Q10 deficiency. Neurology 1997;48:1238–43.10.1212/WNL.48.5.1238Search in Google Scholar
10. Doimo M, Desbats MA, Cerqua C, Cassina M, Trevisson E, et al. Genetics of coenzyme q10 deficiency. Mol Syndromol 2014;5:156–62.10.1159/000362826Search in Google Scholar PubMed PubMed Central
11. Danhauser K, Herebian D, Haack TB, Rodenburg RJ, Strom TM, et al. Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9. Eur J Hum Genet 2016;24:450–4.10.1038/ejhg.2015.133Search in Google Scholar PubMed PubMed Central
12. Multiple-System Atrophy Research C. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 2013;369:233–44.10.1056/NEJMoa1212115Search in Google Scholar PubMed
13. Rahman S, Hargreaves I, Clayton P, Heales S. Neonatal presentation of coenzyme Q10 deficiency. J Pediatr 2001;139:456–8.10.1067/mpd.2001.117575Search in Google Scholar PubMed
14. Molyneux SL, Young JM, Florkowski CM, Lever M, George PM. Coenzyme Q10: is there a clinical role and a case for measurement? Clin Biochem Rev 2008;29:71–82.Search in Google Scholar
15. El-Hattab AW, Scaglia F. Mitochondrial cardiomyopathies. Front Cardiovasc Med 2016;3:25.10.3389/fcvm.2016.00025Search in Google Scholar PubMed PubMed Central
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Articles in the same Issue
- Frontmatter
- Editorial
- Inborn errors of metabolism
- Reviews
- Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs)
- The association between prenatal exposure to organochlorine compounds and neonatal thyroid hormone levels: a systematic review
- Original Articles
- Investigating the incidence rate and geographical distribution of congenital hypothyroidism among neonates in Isfahan province using geographic information system (GIS) between 2002 and 2015
- Analysis of five cases of hypermethioninemia diagnosed by neonatal screening
- What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature
- Machine learning-based prediction of response to growth hormone treatment in Turner syndrome: the LG Growth Study
- Pathogenic/likely pathogenic variants in the SHOX, GHR and IGFALS genes among Indian children with idiopathic short stature
- Celiac disease in Saudi children with isolated short stature: is it rare or are we not screening rigorously enough?
- The beneficial effect of psychological support on mothers with PKU children who suffer from social discrimination and damage of quality of life
- Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty
- Sudden sex hormone withdrawal and the effects on body composition in late pubertal adolescents with gender dysphoria
- The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy
- BMI relationship to the onset of puberty: assessment of growth parameters and sexual maturity changes in Egyptian children and adolescents of both sexes
- The effects of a 12-week jump rope exercise program on body composition, insulin sensitivity, and academic self-efficacy in obese adolescent girls
- Onset of pituitary hormone deficiencies in optic nerve hypoplasia: a temporal trend analysis of 32 children at Mayo Clinic
- Dietary practices in methylmalonic acidaemia: a European survey
- Case Reports
- Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13
- A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation
- Sinusitis, an under-reported adverse effect in children treated with radioactive iodine therapy and review of the current literature
- Acknowledgment
Articles in the same Issue
- Frontmatter
- Editorial
- Inborn errors of metabolism
- Reviews
- Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs)
- The association between prenatal exposure to organochlorine compounds and neonatal thyroid hormone levels: a systematic review
- Original Articles
- Investigating the incidence rate and geographical distribution of congenital hypothyroidism among neonates in Isfahan province using geographic information system (GIS) between 2002 and 2015
- Analysis of five cases of hypermethioninemia diagnosed by neonatal screening
- What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature
- Machine learning-based prediction of response to growth hormone treatment in Turner syndrome: the LG Growth Study
- Pathogenic/likely pathogenic variants in the SHOX, GHR and IGFALS genes among Indian children with idiopathic short stature
- Celiac disease in Saudi children with isolated short stature: is it rare or are we not screening rigorously enough?
- The beneficial effect of psychological support on mothers with PKU children who suffer from social discrimination and damage of quality of life
- Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty
- Sudden sex hormone withdrawal and the effects on body composition in late pubertal adolescents with gender dysphoria
- The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy
- BMI relationship to the onset of puberty: assessment of growth parameters and sexual maturity changes in Egyptian children and adolescents of both sexes
- The effects of a 12-week jump rope exercise program on body composition, insulin sensitivity, and academic self-efficacy in obese adolescent girls
- Onset of pituitary hormone deficiencies in optic nerve hypoplasia: a temporal trend analysis of 32 children at Mayo Clinic
- Dietary practices in methylmalonic acidaemia: a European survey
- Case Reports
- Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13
- A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation
- Sinusitis, an under-reported adverse effect in children treated with radioactive iodine therapy and review of the current literature
- Acknowledgment
