Alternative titles; symbols
SNOMEDCT: 230246005; ICD10CM: G12.1; ORPHA: 97229; DO: 0080632;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20p13 | ?Fazio-Londe disease | 211500 | Autosomal recessive | 3 | SLC52A3 | 613350 |
A number sign (#) is used with this entry because of evidence that Fazio-Londe disease is caused by homozygous mutation in the C20ORF54 gene (SLC52A3; 613350) on chromosome 20p13. One such family has been reported.
Mutations in the SLC52A3 gene also cause Brown-Vialetto-Van Laere syndrome (BVVLS; 211530), a similar disorder with the additional feature of sensorineural hearing loss.
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).
Londe (1894) reported affected 5- and 6-year-old brothers whose parents were first cousins. Marinesco (1915) described it in a 12-year-old girl and her 8-year-old brother. Pyramidal tracts were not involved. Fazio's cases are said (Gomez et al., 1962) to have been a mother and her 4.5-year-old son.
Benjamins (1980) described an identically affected sib of the child reported by Gomez et al. (1962). The boy had been seen at age 29 months because of progressive inspiratory stridor. He showed mild bilateral ptosis and almost immobile vocal cords. At 32 months he had difficulty swallowing, ptosis, bilateral facial weakness, absent gag reflex, generalized hyperreflexia and diminished diaphragmatic motion. He died at 36 months of age; the sib had died at 44 months. The disorder showed phenotypic overlap with amyotrophic lateral sclerosis (ALS; 105400).
Bosch et al. (2011) reported 2 sibs from a consanguineous family. The first child, a boy, presented at 6 months of age with a short history of progressive muscle weakness followed by life-threatening apneic spells requiring ventilation. He had generalized muscle weakness, severe head lag, and diaphragmatic paralysis. His sister presented at 3 months of age with failure to thrive and generalized axial muscle weakness. Sensorineural hearing loss was excluded by brainstem-evoked response audiometry.
The proband of the consanguineous family with Fazio-Londe disease reported by Bosch et al. (2011) had an acylcarnitine profile suggestive of multiple acyl-CoA dehydrogenase deficiency (MADD; 231680), with an abnormal concentration of short- and medium-chain moieties.
Because of the possibility of riboflavin responsiveness, the first patient of Bosch et al. (2011) was treated with high-dose riboflavin (vitamin B2, 10 mg/kg per day). The MADD-associated metabolic abnormalities disappeared within days and the patient's muscle tone slowly improved over the next month. He was able to walk independently at age 22 months. The diaphragmatic paralysis persisted and he required nightly ventilation until 41 months of age. At 46 months of age his cognitive development was normal, and he demonstrated no further cranial nerve palsy. Based on these results, the patient's sister was also treated with riboflavin. She experienced normalization of muscle tone within 7 days and rapid catch-up growth. After 3 months of riboflavin supplementation, her growth and development were normal.
Bosch et al. (2011) identified a consanguineous family with 2 affected children who were found to be homozygous for a splice site mutation in the C20ORF54 gene (613350.0008). Spinal muscular atrophy (SMA; 253300) had been excluded by genetic testing.
Benjamins, D. Progressive bulbar palsy of childhood in siblings. Ann. Neurol. 8: 203 only, 1980. [PubMed: 7425580] [Full Text: https://doi.org/10.1002/ana.410080219]
Bosch, A. M., Abeling, N. G. G. M., IJlst, L., Knoester, H., van der Pol., W. L., Stroomer, A. E. M., Wanders, R. J., Visser, G., Wijburg, F. A., Duran, M., Waterham, H. R. 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. J. Inherit. Metab. Dis. 34: 159-164, 2011. [PubMed: 21110228] [Full Text: https://doi.org/10.1007/s10545-010-9242-z]
Gomez, M. R., Clermont, V., Bernstein, J. Progressive bulbar paralysis in childhood (Fazio-Londe's disease). Report of a case with pathologic evidence of nuclear atrophy. Arch. Neurol. 6: 317-323, 1962. [PubMed: 13900073] [Full Text: https://doi.org/10.1001/archneur.1962.00450220059009]
Londe, P. Paralysie bulbaire progressive, infantile et familiale. Rev. Med. 14: 212-254, 1894.
Marinesco, G. Sur deux cas de paralysie bulbaire progressive infantile et familiale. Comp. Rend. Soc. Biol. 78: 481-483, 1915.