Friedreich ataxia 1

General Information (adopted from Orphanet):

Synonyms, Signs: FRDA1
FRDA
FA Friedreich ataxia with retained reflexes, included
FARR, included
Number of Symptoms 79
OrphanetNr:
OMIM Id: 229300
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Monogenic
Autosomal recessive
23859346 [IBIS]
Age of onset: Childhood, Adolescent
23859346 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Friedreich ataxia
 -Rare cardiac disease
 -Rare eye disease
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Is caused by mutation in the gene encoding frataxin (FXN). 2% of cases of Friedreich ataxia are due to point mutations in the FXN gene, the other 98% being due to expansion of a GAA trinucleotide repeat in intron 1 of the FXN gene (OMIM). A form of monogenic diabetes caused by mutations in FXN (PMID:21127150).

Symptom Information: Sort by abundance 

1
(HPO:0002839) Urinary bladder sphincter dysfunction Occasional [IBIS] 23859346; 10633128 IBIS 34 / 7739
2
(HPO:0004409) Hyposmia 23859346 IBIS 16 / 7739
3
(HPO:0000639) Nystagmus Frequent [IBIS] 23859346 IBIS 555 / 7739
4
(HPO:0001123) Visual field defect Occasional [IBIS] 23859346 IBIS 30 / 7739
5
(HPO:0000649) Abnormality of visual evoked potentials Occasional [IBIS] 23859346 IBIS 34 / 7739
6
(HPO:0000505) Visual impairment rare [HPO] Occasional [IBIS] 23859346; 10633128 IBIS 297 / 7739
7
(HPO:0000648) Optic atrophy 23859346 IBIS 238 / 7739
8
(HPO:0000496) Abnormality of eye movement Occasional [IBIS] 23859346 IBIS 79 / 7739
9
(HPO:0000543) Optic disc pallor Occasional [IBIS] 23859346 IBIS 67 / 7739
10
(HPO:0000508) Ptosis Occasional [IBIS] 23859346 IBIS 459 / 7739
11
(HPO:0000570) Abnormality of saccadic eye movements 23859346 IBIS 12 / 7739
12
(HPO:0000365) Hearing impairment Occasional [IBIS] 23859346; 10633128 IBIS 539 / 7739
13
(HPO:0002270) Abnormality of the autonomic nervous system 23859346 IBIS 22 / 7739
14
(HPO:0002078) Truncal ataxia 23859346 IBIS 41 / 7739
15
(HPO:0001350) Slurred speech 23859346 IBIS 16 / 7739
16
(HPO:0010831) Impaired proprioception 10633128 IBIS 7 / 7739
17
(HPO:0009830) Peripheral neuropathy 23859346 IBIS 206 / 7739
18
(HPO:0003474) Sensory impairment 23859346 IBIS 54 / 7739
19
(HPO:0002522) Areflexia of lower limbs Very frequent [IBIS] 23859346 IBIS 16 / 7739
20
(HPO:0007256) Abnormal pyramidal signs 23859346 IBIS 116 / 7739
21
(HPO:0002070) Limb ataxia Very frequent [IBIS] 23859346; 10633128 IBIS 41 / 7739
22
(HPO:0003487) Babinski sign Frequent [IBIS] 23859346; 10633128 IBIS 179 / 7739
23
(HPO:0006944) Abolished vibration sense Frequent [IBIS] 23859346 IBIS 2 / 7739
24
(HPO:0002311) Incoordination 23859346 IBIS 84 / 7739
25
(HPO:0001251) Ataxia 23859346 IBIS 413 / 7739
26
(HPO:0002066) Gait ataxia Very frequent [IBIS] 23859346; 10633128 IBIS 327 / 7739
27
(HPO:0003448) Decreased sensory nerve conduction velocity 23859346 IBIS 9 / 7739
28
(HPO:0002495) Impaired vibratory sensation 23859346; 10633128 IBIS 26 / 7739
29
(HPO:0000763) Sensory neuropathy 23859346 IBIS 78 / 7739
30
(HPO:0001315) Reduced tendon reflexes 23859346 IBIS 160 / 7739
31
(HPO:0002015) Dysphagia Occasional [IBIS] 23859346 IBIS 301 / 7739
32
(HPO:0002075) Dysdiadochokinesis Very frequent [IBIS] 23859346 IBIS 40 / 7739
33
(HPO:0002403) Positive Romberg sign 23859346 IBIS 11 / 7739
34
(HPO:0002312) Clumsiness 23859346 IBIS 28 / 7739
35
(HPO:0007078) Decreased amplitude of sensory action potentials 23859346 IBIS 5 / 7739
36
(HPO:0001260) Dysarthria Very frequent [IBIS] 23859346; 10633128 IBIS 329 / 7739
37
(HPO:0000819) Diabetes mellitus Occasional [IBIS] 23859346; 23859345; 10633128 IBIS 131 / 7739
38
(HPO:0002751) Kyphoscoliosis 23859346 IBIS 131 / 7739
39
(HPO:0002650) Scoliosis Frequent [IBIS] 23859346; 10633128 IBIS 705 / 7739
40
(HPO:0002808) Kyphosis 23859346 IBIS 289 / 7739
41
(HPO:0010219) Structural foot deformity Frequent [IBIS] 23859346 IBIS 1 / 7739
42
(HPO:0001762) Talipes equinovarus 23859346 IBIS 309 / 7739
43
(HPO:0001763) Pes planus Occasional [IBIS] 23859346 IBIS 176 / 7739
44
(HPO:0009129) Upper limb amyotrophy Frequent [IBIS] 23859346 IBIS 3 / 7739
45
(HPO:0001761) Pes cavus Frequent [IBIS] 23859346; 10633128 IBIS 225 / 7739
46
(HPO:0004326) Cachexia 23859346 IBIS 71 / 7739
47
(HPO:0006089) Palmar hyperhidrosis 23859346 IBIS 5 / 7739
48
(HPO:0003115) Abnormal EKG Frequent [IBIS] 23859346 IBIS 44 / 7739
49
(HPO:0001712) Left ventricular hypertrophy 23859346 IBIS 76 / 7739
50
(HPO:0001670) Asymmetric septal hypertrophy Occasional [IBIS] 23859346 IBIS 19 / 7739
51
(HPO:0010872) EKG: T-wave inversion 23859346 IBIS 19 / 7739
52
(HPO:0011703) Sinus tachycardia 23859346 IBIS 5 / 7739
53
(HPO:0003116) Abnormal echocardiogram 23859346 IBIS 33 / 7739
54
(HPO:0001639) Hypertrophic cardiomyopathy 23859346 IBIS 137 / 7739
55
(HPO:0006673) Reduced systolic function 23859346 IBIS 11 / 7739
56
(HPO:0005110) Atrial fibrillation 23859346 IBIS 71 / 7739
57
(HPO:0001638) Cardiomyopathy Frequent [IBIS] 23859346; 10633128 IBIS 192 / 7739
58
(HPO:0001635) Congestive heart failure 23859346 IBIS 232 / 7739
59
(HPO:0011675) Arrhythmia 23859346 IBIS 226 / 7739
60
(HPO:0001644) Dilated cardiomyopathy Occasional [IBIS] 23859346 IBIS 141 / 7739
61
(HPO:0011025) Abnormality of cardiovascular system physiology 23859346 IBIS 41 / 7739
62
(HPO:0000833) Glucose intolerance 23859346; 23859345 IBIS 20 / 7739
63
(HPO:0000855) Insulin resistance 23859346 IBIS 32 / 7739
64
(HPO:0001993) Ketoacidosis 23859345 IBIS 17 / 7739
65
(HPO:0003209) Decreased pyruvate carboxylase activity 6847147 IBIS 5 / 7739
66
(HPO:0003232) Mitochondrial malic enzyme reduced 7199631 IBIS 4 / 7739
67
(HPO:0007210) Lower limb amyotrophy Frequent [IBIS] 23859346 IBIS 7 / 7739
68
(HPO:0007340) Lower limb muscle weakness Frequent [IBIS] 23859346; 10633128 IBIS 61 / 7739
69
(HPO:0100321) Abnormality of the dentate nucleus 23859346 IBIS 3 / 7739
70
(MedDRA:10061330) Papillary muscle disorder 23859346 IBIS 1 / 7739
71
(HPO:0008311) Spinal cord posterior columns myelin loss 23859346 IBIS 2 / 7739
72
(MedDRA:10048815) Sinus rhythm 23859346 IBIS 3 / 7739
73
(OMIM) Cold feet 23859346 IBIS 2 / 7739
74
(MedDRA:10052337) Diastolic dysfunction 23859346 IBIS 14 / 7739
75
(HPO:0002503) Spinocerebellar tract degeneration 23859346 IBIS 8 / 7739
76
(HPO:0001272) Cerebellar atrophy 23859346 IBIS 197 / 7739
77
(MedDRA:10056997) Impaired fasting glucose 23859345 IBIS 1 / 7739
78
(MedDRA:10052341) Impaired insulin secretion 23859346 IBIS 3 / 7739
79
(HPO:0030286) Atrophic superior cerebellar peduncle 23859346 IBIS 1 / 7739

Associated genes:

FXN;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
FXN rs104894105 pathogenic RCV000004186.2
FXN rs104894106 pathogenic RCV000004188.2
FXN rs104894107 pathogenic RCV000004189.2
FXN rs104894108 pathogenic RCV000004190.2
FXN rs140987490 pathogenic RCV000004187.2
FXN rs56214919 likely pathogenic RCV000004191.1

Additional Information:

Description: (OMIM) Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in ...
Clinical Description OMIM In FRDA, the spinocerebellar tracts, dorsal columns, pyramidal tracts and, to a lesser extent, the cerebellum and medulla are involved. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, ...
Genotype-Phenotype Correlations OMIM Filla et al. (1996) studied the relationship between the trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. The length of the FA alleles ranged from 201 to 1,186 repeat units. There was no overlap between the ...
Molecular genetics OMIM Delatycki et al. (1999) stated that 2% of cases of Friedreich ataxia are due to point mutations in the FXN gene (606829), the other 98% being due to expansion of a GAA trinucleotide repeat in intron 1 of ...
Population genetics OMIM Friedreich ataxia occurs with a prevalence of approximately 1/50,000 in Caucasian populations, but is rare among sub-Saharan Africans and does not exist in the Far East (Koenig, 1998). Dean et al. (1988) found a particularly high frequency of ...