FALOND
MCID: FZL002
MIFTS: 44

Fazio-Londe Disease (FALOND)

Categories: Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Fazio-Londe Disease

MalaCards integrated aliases for Fazio-Londe Disease:

Name: Fazio-Londe Disease 56 12 25 73 13 15
Fazio-Londe Syndrome 74 25 73 71
Riboflavin Transporter Deficiency Neuronopathy 12 24 25
Progressive Bulbar Palsy of Childhood 29 6
Brown-Vialetto-Van Laere Syndrome 25 58
Riboflavin Transporter Deficiency 25 58
Sensorineural Hearing Loss-Pontobulbar Palsy Syndrome 58
Progressive Bulbar Palsy with Sensorineural Deafness 25
Sensorineural Deafness-Pontobulbar Palsy Syndrome 58
Bulbar Palsy, Progressive, of Childhood 56
Bulbar Palsy of Childhood, Progressive 39
Bulbar Palsy Progressive of Childhood 73
Pontobulbar Palsy with Deafness 25
Falond 73
Bvvls 25

Characteristics:

Orphanet epidemiological data:

58
riboflavin transporter deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
fazio-londe disease:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare otorhinolaryngological diseases
Developmental anomalies during embryogenesis


Summaries for Fazio-Londe Disease

Genetics Home Reference : 25 Riboflavin transporter deficiency neuronopathy is a disorder that affects nerve cells (neurons). Affected individuals typically have hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and signs of damage to other nerves. In addition to nerves in the inner ear, riboflavin transporter deficiency neuronopathy involves nerves found in the part of the brain that is connected to the spinal cord (the brainstem), specifically in a region of the brainstem known as the pontobulbar region. Damage to these nerves causes paralysis of the muscles controlled by them, a condition called pontobulbar palsy. Nerves in the pontobulbar region help control several voluntary muscle activities, including breathing, speaking, and moving the limbs. As a result of pontobulbar palsy, people with riboflavin transporter deficiency neuronopathy can have breathing problems; slurred speech; and muscle weakness in the face, neck, shoulders, and limbs. Affected individuals can also have muscle stiffness (spasticity) and exaggerated reflexes. The age at which riboflavin transporter deficiency neuronopathy begins varies from infancy to young adulthood. When the condition begins in infancy, the first symptom is often breathing problems caused by nerve damage, which can be life-threatening. When the condition begins in children or young adults, sensorineural hearing loss usually occurs first, followed by signs of pontobulbar palsy. If not treated, the signs and symptoms of riboflavin transporter deficiency neuronopathy worsen over time. Severe breathing problems and respiratory infections are the usual cause of death in people with this condition. Without treatment, affected infants typically survive less than one year. However, those who develop the condition after age 4 often survive more than 10 years. Riboflavin transporter deficiency neuronopathy encompasses two conditions that were once considered distinct disorders: Brown-Vialetto-Van Laere syndrome (BVVLS) and Fazio-Londe disease. The two conditions have similar signs and symptoms, but Fazio-Londe disease does not include sensorineural hearing loss. Because these two conditions share a genetic cause and have overlapping features, researchers determined that they are forms of a single disorder.

MalaCards based summary : Fazio-Londe Disease, also known as fazio-londe syndrome, is related to brown-vialetto-van laere syndrome 2 and madras motor neuron disease. An important gene associated with Fazio-Londe Disease is SLC52A3 (Solute Carrier Family 52 Member 3), and among its related pathways/superpathways are Metabolism and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include tongue, brain and spinal cord, and related phenotypes are progressive hearing impairment and bulbar palsy

Disease Ontology : 12 A progressive bulbar palsy that is characterized by motor, sensory and cranial neuronopathy and that has material basis in homozygous mutation in the C20ORF54 gene on chromosome 20p13.

OMIM : 56 Fazio-Londe disease is a progressive bulbar palsy with onset in childhood that presents with hypotonia and respiratory insufficiency (summary by Bosch et al., 2011). (211500)

UniProtKB/Swiss-Prot : 73 Fazio-Londe disease: A rare neurological disease characterized by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. It may present in childhood with severe neurological deterioration with hypotonia, respiratory insufficiency leading to premature death, or later in life with bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles.

Wikipedia : 74 Fazio-Londe disease (FLD), also called progressive bulbar palsy of childhood, is a very rare inherited... more...

GeneReviews: NBK299312

Related Diseases for Fazio-Londe Disease

Diseases related to Fazio-Londe Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 64)
# Related Disease Score Top Affiliating Genes
1 brown-vialetto-van laere syndrome 2 35.4 SLC52A3 SLC52A2
2 madras motor neuron disease 33.3 SLC52A3 SLC52A2 SLC52A1
3 brown-vialetto-van laere syndrome 1 30.9 SLC52A3 SLC52A2
4 cranial nerve palsy 30.8 SLC52A3 SLC52A2 SLC52A1
5 motor neuron disease 30.7 SLC52A3 SLC52A2 SLC52A1
6 brown-vialetto-van laere syndrome 29.5 TMCO4 SLC52A3 SLC52A2 SLC52A1 FLAD1 FAM187B
7 progressive bulbar palsy 29.1 TMCO4 SLC52A3 SLC52A2 SLC52A1 FAM187B ETFDH
8 multiple acyl-coa dehydrogenase deficiency 29.1 SLC52A3 SLC52A2 SLC52A1 FLAD1 ETFDH ETFB
9 riboflavin deficiency 29.1 SLC52A3 SLC52A2 SLC52A1 FLAD1 ETFDH ETFB
10 myopathy 27.5 NDUFV1 FLAD1 ETFDH ETFB ETFA
11 sensorineural hearing loss 11.1
12 auditory neuropathy spectrum disorder 10.8
13 dysphagia 10.8
14 nathalie syndrome 10.7
15 3-methylglutaconic aciduria, type iii 10.7
16 ataxia and polyneuropathy, adult-onset 10.7
17 ptosis 10.7
18 multiple cranial nerve palsy 10.7
19 hypotonia 10.7
20 branchiootic syndrome 1 10.6
21 dowling-degos disease 1 10.5
22 retinitis pigmentosa 10.5
23 pulmonary hypertension 10.5
24 sleep apnea 10.5
25 cardiac arrest 10.5
26 neuroretinitis 10.5
27 polyneuropathy 10.5
28 toxic shock syndrome 10.5
29 status epilepticus 10.5
30 retinitis 10.5
31 central sleep apnea 10.5
32 autonomic dysfunction 10.5
33 neurometabolic disease 10.5
34 facial paralysis 10.4
35 amyotrophic lateral sclerosis 1 10.4
36 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.4
37 respiratory failure 10.4
38 spinal muscular atrophy 10.4
39 lateral sclerosis 10.4
40 axonal neuropathy 10.4
41 muscular atrophy 10.4
42 neuropathy 10.4
43 giant axonal neuropathy 10.4
44 juvenile amyotrophic lateral sclerosis 10.4
45 scoliosis 10.2
46 chronic apical periodontitis 10.2 SLC52A3 SLC52A2
47 acyl-coa dehydrogenase, short-chain, deficiency of 10.0 ETFDH ETFA
48 glutaric acidemia i 9.9 ETFDH ETFA
49 charcot-marie-tooth disease, demyelinating, type 1a 9.9
50 breath-holding spells 9.9

Graphical network of the top 20 diseases related to Fazio-Londe Disease:



Diseases related to Fazio-Londe Disease

Symptoms & Phenotypes for Fazio-Londe Disease

Human phenotypes related to Fazio-Londe Disease:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0001730
2 bulbar palsy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001283
3 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
4 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
5 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
6 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
7 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
8 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
9 abnormality of eye movement 58 31 frequent (33%) Frequent (79-30%) HP:0000496
10 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
11 facial palsy 58 31 frequent (33%) Frequent (79-30%) HP:0010628
12 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
13 limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003690
14 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
15 hallucinations 58 31 occasional (7.5%) Occasional (29-5%) HP:0000738
16 visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000505
17 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
18 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
19 cachexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0004326
20 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
21 diabetes insipidus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000873
22 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
23 gynecomastia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000771
24 sleep apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0010535
25 color vision defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0000551
26 iris hypopigmentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0007730
27 optic disc pallor 58 31 occasional (7.5%) Occasional (29-5%) HP:0000543
28 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135
29 aggressive behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0000718
30 abnormality of macular pigmentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0008002
31 abnormal autonomic nervous system physiology 31 occasional (7.5%) HP:0012332
32 seizure 31 occasional (7.5%) HP:0001250
33 seizures 58 Occasional (29-5%)
34 muscle weakness 58 Frequent (79-30%)
35 cranial nerve paralysis 58 Very frequent (99-80%)
36 abnormal cranial nerve morphology 58 Very frequent (99-80%)
37 diaphragmatic weakness 31 HP:0009113
38 dysautonomia 58 Occasional (29-5%)
39 generalized hyperreflexia 31 HP:0007034
40 facial diplegia 31 HP:0001349
41 progressive inspiratory stridor 31 HP:0005951

Symptoms via clinical synopsis from OMIM:

56
Eyes:
ptosis

Respiratory:
progressive inspiratory stridor
diminished diaphragmatic motion

Neuro:
bulbar palsy
generalized hyperreflexia
absent gag reflex
swallowing difficulty
bilateral facial weakness
more

Clinical features from OMIM:

211500

GenomeRNAi Phenotypes related to Fazio-Londe Disease according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased POU5F1-GFP protein expression GR00184-A-1 8.92 ETFDH NDUFV1 PPOX SLC52A1

Drugs & Therapeutics for Fazio-Londe Disease

Search Clinical Trials , NIH Clinical Center for Fazio-Londe Disease

Genetic Tests for Fazio-Londe Disease

Genetic tests related to Fazio-Londe Disease:

# Genetic test Affiliating Genes
1 Progressive Bulbar Palsy of Childhood 29 SLC52A3

Anatomical Context for Fazio-Londe Disease

MalaCards organs/tissues related to Fazio-Londe Disease:

40
Tongue, Brain, Spinal Cord, Eye, Skeletal Muscle

Publications for Fazio-Londe Disease

Articles related to Fazio-Londe Disease:

(show top 50) (show all 77)
# Title Authors PMID Year
1
Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. 56 6 24 61
21110228 2011
2
Brown-Vialetto-Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease. 61 24 6
16122634 2005
3
Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. 24 6
24253200 2014
4
Riboflavin transporter 3 involvement in infantile Brown-Vialetto-Van Laere disease: two novel mutations. 6 24
23243084 2013
5
Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome. 6 24
22864630 2012
6
Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. 6 24
22740598 2012
7
Exome sequencing in Brown-Vialetto-van Laere syndrome. 24 6
20920669 2010
8
Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. 6 24
20206331 2010
9
Brown-Vialetto-Van Laere syndrome in a large inbred Lebanese family: confirmation of autosomal recessive inheritance? 24 6
10797435 2000
10
Progressive bulbar paralysis in childhood (Fazio-Londe's disease). Report of a case with pathologic evidence of nuclear atrophy. 24 56
13900073 1962
11
Riboflavin Transporter Deficiency Neuronopathy 6
26072523 2015
12
Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome. 61 24
24139842 2013
13
The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives. 24 61
23107375 2012
14
Four novel C20orf54 mutations identified in Brown-Vialetto-Van Laere syndrome patients. 61 24
22718020 2012
15
Brown-Vialetto-Van Laere syndrome. 24 61
18416855 2008
16
Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease. 24 61
1486466 1992
17
Progressive bulbar paralysis of childhood (Fazio-Londe disease) with deafness. Case report with clinicopathologic correlation. 61 24
7094955 1982
18
Progressive bulbar palsy of childhood in siblings. 56
7425580 1980
19
Progressive bulbar paresis in childhood. 24 61
1247398 1976
20
Spectrum of metabolic myopathies. 24
24997454 2015
21
Mutations in riboflavin transporter present with severe sensory loss and deafness in childhood. 24
24616084 2014
22
Replication of results of genome-wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population. 24
24152165 2014
23
Recent advances in bulbar syndromes: genetic causes and disease mechanisms. 24
25159929 2014
24
Heterozygous D90A-SOD1 mutation in a patient with facial onset sensory motor neuronopathy (FOSMN) syndrome: a bridge to amyotrophic lateral sclerosis. 24
24591457 2014
25
Brown-Vialetto-van Laere syndrome: a riboflavin responsive neuronopathy of infancy with singular features. 24
24206674 2014
26
Brown-Vialetto-Van Laere syndrome: clinical and neuroradiological findings of a genetically proven patient. 24
24079556 2014
27
Maternal dietary nutrient intake and risk of preterm delivery. 24
23208764 2013
28
Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. 24
23506902 2013
29
[The relationship between C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma]. 24
23327963 2012
30
Association of UBQLN1 mutation with Brown-Vialetto-Van Laere syndrome but not typical ALS. 24
22766032 2012
31
Genetic variation in C20orf54, PLCE1 and MUC1 and the risk of upper gastrointestinal cancers in Caucasian populations. 24
22805490 2012
32
FOSMN syndrome: novel insight into disease pathophysiology. 24
22722633 2012
33
Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10). 24
22231380 2012
34
Effect of clinical mutations on functionality of the human riboflavin transporter-2 (hRFT-2). 24
22273710 2012
35
Clinical diagnosis and management of amyotrophic lateral sclerosis. 24
21989247 2011
36
Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric aciduria Type 2, is caused by a microdeletion in the riboflavin transporter gene GPR172B. 24
21089064 2011
37
Pontobulbar palsy and sensorineural deafness (Brown-Vialetto-van Laere syndrome): the first case from Libya. 24
20001484 2010
38
Novel mutations in ETFDH gene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. 24
19265687 2009
39
The small, spastic, and furrowed tongue of Allgrove syndrome. 24
19365062 2009
40
Adolescent spinal muscular atrophy with calf hypertrophy and a deletion in the SMN gene. 24
18508340 2008
41
Severe sleep-disordered breathing in a patient with Brown-Vialetto-Van Laere syndrome: polysomnographic findings. 24
17669429 2007
42
Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. 24
17689999 2007
43
ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. 24
17584774 2007
44
A Brazilian family with Brown-Vialetto-van Laere syndrome with autosomal recessive inheritance. 24
17420823 2007
45
Cardiac arrest in a patient with Brown-Vialetto-Van Laere syndrome. 24
16963409 2006
46
Clinical and genetic characterization of families with triple A (Allgrove) syndrome. 24
12429595 2002
47
Infantile progressive bulbar palsy with deafness. 24
12427524 2002
48
Brown-Vialetto-Van Laere syndrome: case report and literature review. 24
11465021 2000
49
Riboflavin deficiency and preeclampsia. 24
10862839 2000
50
Pathology of Madras type of motor neuron disease (MMND)--a histological and immunohistochemical study. 24
10787043 2000

Variations for Fazio-Londe Disease

ClinVar genetic disease variations for Fazio-Londe Disease:

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLC52A3 NM_033409.4(SLC52A3):c.1198-2A>CSNV Pathogenic 210025 rs754753126 20:741884-741884 20:761240-761240
2 SLC52A3 NM_033409.4(SLC52A3):c.71G>A (p.Trp24Ter)SNV Likely pathogenic 800969 20:746348-746348 20:765704-765704

Expression for Fazio-Londe Disease

Search GEO for disease gene expression data for Fazio-Londe Disease.

Pathways for Fazio-Londe Disease

GO Terms for Fazio-Londe Disease

Cellular components related to Fazio-Londe Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.5 PPOX NDUFV1 FLAD1 ETFDH ETFB ETFA
2 mitochondrial membrane GO:0031966 9.33 PPOX ETFDH ACADL
3 integral component of mitochondrial inner membrane GO:0031305 9.26 PPOX ETFDH
4 mitochondrial matrix GO:0005759 9.02 FLAD1 ETFDH ETFB ETFA ACADL

Biological processes related to Fazio-Londe Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.8 PPOX NDUFV1 ETFDH ETFB ETFA ACADL
2 electron transport chain GO:0022900 9.54 ETFDH ETFB ETFA
3 respiratory electron transport chain GO:0022904 9.43 ETFDH ETFB ETFA
4 riboflavin transport GO:0032218 9.33 SLC52A3 SLC52A2 SLC52A1
5 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.26 ETFDH ETFB ETFA ACADL
6 riboflavin metabolic process GO:0006771 8.92 SLC52A3 SLC52A2 SLC52A1 FLAD1

Molecular functions related to Fazio-Londe Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.55 PPOX NDUFV1 ETFDH ETFA ACADL
2 electron transfer activity GO:0009055 9.43 ETFDH ETFB ETFA
3 virus receptor activity GO:0001618 9.4 SLC52A2 SLC52A1
4 iron-sulfur cluster binding GO:0051536 9.37 NDUFV1 ETFDH
5 4 iron, 4 sulfur cluster binding GO:0051539 9.32 NDUFV1 ETFDH
6 flavin adenine dinucleotide binding GO:0050660 9.26 PPOX ETFDH ETFA ACADL
7 riboflavin transmembrane transporter activity GO:0032217 8.8 SLC52A3 SLC52A2 SLC52A1

Sources for Fazio-Londe Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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