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Coenzyme q10 deficiency, primary, 9(COQ10D9)

MedGen UID:
1740444
Concept ID:
C5436638
Disease or Syndrome
Synonyms: COENZYME Q10 DEFICIENCY, PRIMARY, 9; COQ10D9
 
Gene (location): COQ5 (12q24.31)
 
Monarch Initiative: MONDO:0033615
OMIM®: 619028

Definition

Coenzyme Q10 deficiency-9 (COQ10D9) is an autosomal recessive disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in the first decade of life. Some patients may have additional neurologic signs and symptoms, including intellectual disability and seizures. Treatment with CoQ10 may offer clinical benefit (summary by Malicdan et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426). [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Impulsivity
MedGen UID:
43850
Concept ID:
C0021125
Mental or Behavioral Dysfunction
Acting on the spur of the moment or on a momentary basis without consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in behavior that is uninhibited, cannot be inhibited, and is uncontrolled. The possibility of repression is inconceivable.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Oppositional defiant disorder
MedGen UID:
18178
Concept ID:
C0029121
Mental or Behavioral Dysfunction
An enduring pattern of uncooperative, defiant, and hostile behavior towards authority figures that does not involve major antisocial violations, is not accounted for by the child's developmental stage, and results in significant functional impairment. A certain level of oppositional behavior is common in children and adolescents.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Short attention span
MedGen UID:
82652
Concept ID:
C0262630
Finding
Reduced attention span characterized by distractibility and impulsivity.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Impaired tandem gait
MedGen UID:
476998
Concept ID:
C3275367
Finding
Reduced ability to walk in a straight line while placing the feet heel to toe.
Bilateral tonic-clonic seizure with generalized onset
MedGen UID:
1368929
Concept ID:
C4476643
Sign or Symptom
A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure.
Type 2 muscle fiber predominance
MedGen UID:
478817
Concept ID:
C3277187
Finding
An abnormal predominance of type II muscle fibers (in general, this feature can only be observed on muscle biopsy).
Horizontal nystagmus
MedGen UID:
124399
Concept ID:
C0271385
Disease or Syndrome
Nystagmus consisting of horizontal to-and-fro eye movements.
Hypometric saccades
MedGen UID:
98065
Concept ID:
C0423082
Finding
Saccadic undershoot, i.e., a saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.

Professional guidelines

PubMed

Drovandi S, Lipska-Ziętkiewicz BS, Ozaltin F, Emma F, Gulhan B, Boyer O, Trautmann A, Ziętkiewicz S, Xu H, Shen Q, Rao J, Riedhammer KM, Heemann U, Hoefele J, Stenton SL, Tsygin AN, Ng KH, Fomina S, Benetti E, Aurelle M, Prikhodina L, Schijvens AM, Tabatabaeifar M, Jankowski M, Baiko S, Mao J, Feng C, Deng F, Rousset-Rouviere C, Stańczyk M, Bałasz-Chmielewska I, Fila M, Durkan AM, Levart TK, Dursun I, Esfandiar N, Haas D, Bjerre A, Anarat A, Benz MR, Talebi S, Hooman N, Ariceta G; PodoNet Consortium; mitoNET Consortium; CCGKDD Consortium, Schaefer F
Kidney Int 2022 Sep;102(3):592-603. Epub 2022 Apr 26 doi: 10.1016/j.kint.2022.02.040. PMID: 35483523

Recent clinical studies

Etiology

Nam DW, Park SS, Lee SM, Suh MW, Park MK, Song JJ, Choi BY, Lee JH, Oh SH, Moon KC, Ahn YH, Kang HG, Cheong HI, Kim JH, Lee SY
Biomed Res Int 2022;2022:5250254. Epub 2022 Sep 9 doi: 10.1155/2022/5250254. PMID: 36124066Free PMC Article
Al Saadi T, Assaf Y, Farwati M, Turkmani K, Al-Mouakeh A, Shebli B, Khoja M, Essali A, Madmani ME
Cochrane Database Syst Rev 2021 Feb 3;(2)(2):CD008684. doi: 10.1002/14651858.CD008684.pub3. PMID: 35608922Free PMC Article
Liu G, Ma D, Li J, Luo C, Sun Y, Zhang J, Hu P, Tang W, Xu Z
Clin Biochem 2020 Oct;84:93-98. Epub 2020 Jun 14 doi: 10.1016/j.clinbiochem.2020.06.010. PMID: 32553579
Cerqua C, Casarin A, Pierrel F, Vazquez Fonseca L, Viola G, Salviati L, Trevisson E
Sci Rep 2019 Apr 25;9(1):6553. doi: 10.1038/s41598-019-43014-y. PMID: 31024065Free PMC Article
Desbats MA, Vetro A, Limongelli I, Lunardi G, Casarin A, Doimo M, Spinazzi M, Angelini C, Cenacchi G, Burlina A, Rodriguez Hernandez MA, Chiandetti L, Clementi M, Trevisson E, Navas P, Zuffardi O, Salviati L
Eur J Hum Genet 2015 Sep;23(9):1254-8. Epub 2015 Jan 7 doi: 10.1038/ejhg.2014.277. PMID: 25564041Free PMC Article

Diagnosis

Nam DW, Park SS, Lee SM, Suh MW, Park MK, Song JJ, Choi BY, Lee JH, Oh SH, Moon KC, Ahn YH, Kang HG, Cheong HI, Kim JH, Lee SY
Biomed Res Int 2022;2022:5250254. Epub 2022 Sep 9 doi: 10.1155/2022/5250254. PMID: 36124066Free PMC Article
Drovandi S, Lipska-Ziętkiewicz BS, Ozaltin F, Emma F, Gulhan B, Boyer O, Trautmann A, Ziętkiewicz S, Xu H, Shen Q, Rao J, Riedhammer KM, Heemann U, Hoefele J, Stenton SL, Tsygin AN, Ng KH, Fomina S, Benetti E, Aurelle M, Prikhodina L, Schijvens AM, Tabatabaeifar M, Jankowski M, Baiko S, Mao J, Feng C, Deng F, Rousset-Rouviere C, Stańczyk M, Bałasz-Chmielewska I, Fila M, Durkan AM, Levart TK, Dursun I, Esfandiar N, Haas D, Bjerre A, Anarat A, Benz MR, Talebi S, Hooman N, Ariceta G; PodoNet Consortium; mitoNET Consortium; CCGKDD Consortium, Schaefer F
Kidney Int 2022 Sep;102(3):592-603. Epub 2022 Apr 26 doi: 10.1016/j.kint.2022.02.040. PMID: 35483523
Olgac A, Öztoprak Ü, Kasapkara ÇS, Kılıç M, Yüksel D, Derinkuyu EB, Taşçı Yıldız Y, Ceylaner S, Ezgu FS
J Pediatr Endocrinol Metab 2020 Jan 28;33(1):165-170. doi: 10.1515/jpem-2019-0245. PMID: 31821167
Starr MC, Chang IJ, Finn LS, Sun A, Larson AA, Goebel J, Hanevold C, Thies J, Van Hove JLK, Hingorani SR, Lam C
Pediatr Nephrol 2018 Jul;33(7):1257-1261. Epub 2018 Apr 10 doi: 10.1007/s00467-018-3937-z. PMID: 29637272Free PMC Article
Desbats MA, Vetro A, Limongelli I, Lunardi G, Casarin A, Doimo M, Spinazzi M, Angelini C, Cenacchi G, Burlina A, Rodriguez Hernandez MA, Chiandetti L, Clementi M, Trevisson E, Navas P, Zuffardi O, Salviati L
Eur J Hum Genet 2015 Sep;23(9):1254-8. Epub 2015 Jan 7 doi: 10.1038/ejhg.2014.277. PMID: 25564041Free PMC Article

Therapy

Al Saadi T, Assaf Y, Farwati M, Turkmani K, Al-Mouakeh A, Shebli B, Khoja M, Essali A, Madmani ME
Cochrane Database Syst Rev 2021 Feb 3;(2)(2):CD008684. doi: 10.1002/14651858.CD008684.pub3. PMID: 35608922Free PMC Article
Starr MC, Chang IJ, Finn LS, Sun A, Larson AA, Goebel J, Hanevold C, Thies J, Van Hove JLK, Hingorani SR, Lam C
Pediatr Nephrol 2018 Jul;33(7):1257-1261. Epub 2018 Apr 10 doi: 10.1007/s00467-018-3937-z. PMID: 29637272Free PMC Article

Prognosis

Olgac A, Öztoprak Ü, Kasapkara ÇS, Kılıç M, Yüksel D, Derinkuyu EB, Taşçı Yıldız Y, Ceylaner S, Ezgu FS
J Pediatr Endocrinol Metab 2020 Jan 28;33(1):165-170. doi: 10.1515/jpem-2019-0245. PMID: 31821167
Smith AC, Ito Y, Ahmed A, Schwartzentruber JA, Beaulieu CL, Aberg E, Majewski J, Bulman DE, Horsting-Wethly K, Koning DV; Care4Rare Canada Consortium, Rodenburg RJ, Boycott KM, Penney LS
J Inherit Metab Dis 2018 Jul;41(4):719-729. Epub 2018 Mar 20 doi: 10.1007/s10545-017-0122-7. PMID: 29560582
Desbats MA, Vetro A, Limongelli I, Lunardi G, Casarin A, Doimo M, Spinazzi M, Angelini C, Cenacchi G, Burlina A, Rodriguez Hernandez MA, Chiandetti L, Clementi M, Trevisson E, Navas P, Zuffardi O, Salviati L
Eur J Hum Genet 2015 Sep;23(9):1254-8. Epub 2015 Jan 7 doi: 10.1038/ejhg.2014.277. PMID: 25564041Free PMC Article

Clinical prediction guides

Drovandi S, Lipska-Ziętkiewicz BS, Ozaltin F, Emma F, Gulhan B, Boyer O, Trautmann A, Ziętkiewicz S, Xu H, Shen Q, Rao J, Riedhammer KM, Heemann U, Hoefele J, Stenton SL, Tsygin AN, Ng KH, Fomina S, Benetti E, Aurelle M, Prikhodina L, Schijvens AM, Tabatabaeifar M, Jankowski M, Baiko S, Mao J, Feng C, Deng F, Rousset-Rouviere C, Stańczyk M, Bałasz-Chmielewska I, Fila M, Durkan AM, Levart TK, Dursun I, Esfandiar N, Haas D, Bjerre A, Anarat A, Benz MR, Talebi S, Hooman N, Ariceta G; PodoNet Consortium; mitoNET Consortium; CCGKDD Consortium, Schaefer F
Kidney Int 2022 Sep;102(3):592-603. Epub 2022 Apr 26 doi: 10.1016/j.kint.2022.02.040. PMID: 35483523
Olgac A, Öztoprak Ü, Kasapkara ÇS, Kılıç M, Yüksel D, Derinkuyu EB, Taşçı Yıldız Y, Ceylaner S, Ezgu FS
J Pediatr Endocrinol Metab 2020 Jan 28;33(1):165-170. doi: 10.1515/jpem-2019-0245. PMID: 31821167
Smith AC, Ito Y, Ahmed A, Schwartzentruber JA, Beaulieu CL, Aberg E, Majewski J, Bulman DE, Horsting-Wethly K, Koning DV; Care4Rare Canada Consortium, Rodenburg RJ, Boycott KM, Penney LS
J Inherit Metab Dis 2018 Jul;41(4):719-729. Epub 2018 Mar 20 doi: 10.1007/s10545-017-0122-7. PMID: 29560582

Recent systematic reviews

Drovandi S, Lipska-Ziętkiewicz BS, Ozaltin F, Emma F, Gulhan B, Boyer O, Trautmann A, Ziętkiewicz S, Xu H, Shen Q, Rao J, Riedhammer KM, Heemann U, Hoefele J, Stenton SL, Tsygin AN, Ng KH, Fomina S, Benetti E, Aurelle M, Prikhodina L, Schijvens AM, Tabatabaeifar M, Jankowski M, Baiko S, Mao J, Feng C, Deng F, Rousset-Rouviere C, Stańczyk M, Bałasz-Chmielewska I, Fila M, Durkan AM, Levart TK, Dursun I, Esfandiar N, Haas D, Bjerre A, Anarat A, Benz MR, Talebi S, Hooman N, Ariceta G; PodoNet Consortium; mitoNET Consortium; CCGKDD Consortium, Schaefer F
Kidney Int 2022 Sep;102(3):592-603. Epub 2022 Apr 26 doi: 10.1016/j.kint.2022.02.040. PMID: 35483523
Al Saadi T, Assaf Y, Farwati M, Turkmani K, Al-Mouakeh A, Shebli B, Khoja M, Essali A, Madmani ME
Cochrane Database Syst Rev 2021 Feb 3;(2)(2):CD008684. doi: 10.1002/14651858.CD008684.pub3. PMID: 35608922Free PMC Article

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