Fazio–Londe disease

Signs and symptoms

FLD produces rapidly progressive weakness of tongue, face and pharyngeal muscles in a clinical pattern similar to myasthenia. Neuromuscular transmission may be abnormal in these muscles because of rapid denervation and immature reinnervation. Paralysis occurs secondary to degeneration of the motor neurons of the brain stem. It causes progressive bulbar paralysis due to involvement of motor neurons of the cranial nerve nuclei. The most frequent symptoms at onset of progressive bulbar paralysis of childhood has been a unilateral facial paralysis. It is followed in frequency by dysarthria due to facial weakness or by dysphagia. Palatal weakness and palpebral ptosis also have been reported in few patients. Both sexes can be affected.

Genetics

Fazio–Londe disease is linked to a genetic mutation in the SLC52A3 gene on chromosome 20 (locus: 20p13). It is allelic and phenotypically similar to Brown–Vialetto–Van Laere syndrome. The condition is inherited in an autosomal recessive manner. The gene encodes the intestinal riboflavin transporter (hRFT2).

Diagnosis

Symptoms of Fazio–Londe include bulbar palsy, hearing loss, facial weakness, and difficulty breathing. The disease is caused by mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) genes which code for hRFT3 and hRFT1, human riboflavin transporters. Only muscle biopsy and examination of the transporter genes is considered to provide a definitive diagnosis. However, because the disease is so often fatal without treatment, and because the treatment is so inexpensive and with little risk, it is recommended that if the disease is suspected that riboflavin therapy be started immediately while testing is in progress.

Treatment

The condition is treatable. High doses of oral riboflavin 5 phosphate may work,

Prognosis

Onset of first symptom has been reported between 1–12 years, with a mean age of onset at 8 years. Clinical course can be divided into early (

The disease may progress to patient's death in a period as short as 9 months or may have a slow evolution or may show plateaus. Postmortem examination of cases have found depletion of nerve cells in the nuclei of cranial nerves. The histologic alterations found in patient with Fazio–Londe disease were identical to those seen in infantile-onset spinal muscular atrophy.

Strength may improve with administration of cholinesterase inhibitors.

History

Berger, in 1876, first reported a case of 12-year-old boy with progressive bulbar paralysis. His medical history revealed a neurological illness with difficulty in swallowing liquids and solids, nasal regurgitation to liquids, nasal twang 2 years ago. He was treated for post-diptheritic bulbar palsy and had a residual bulbar weakness. Other details were not available. The child was ambulant and apparently normal until 3 months back when he developed respiratory distress and was treated at a local hospital prior to referral. He had a past history of dog bite 3 months ago for which he received five doses of anti-rabies vaccine. He was born out of a non-consanguineous marriage. The antenatal, natal, postnatal histories were insignificant. His elder sibling was healthy. This child was immunised appropriate for age. There was no family history of any neurological illness or sibling death.

Eponym

It is named for the Italian pathologist Eugenio Fazio (1849–1902) and the French physician Paul Frederic Louis Londe (1864–1944).

References

References

1. {{OMIM. 211500
2. (December 1992). "Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease.". Brain: A Journal of Neurology.
3. (2013). "Fenichel's Clinical Pediatric Neurology E-Book: A Signs and Symptoms Approach". Elsevier Health Sciences.
4. "OMIM Entry - # 211500 - FAZIO-LONDE DISEASE".
5. "Fazio-Londe Disease - Tests - GTR - NCBI".
6. (September 2005). "Brown–Vialetto–Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio–Londe disease". Brain Dev..
7. "SLC52A3 solute carrier family 52 member 3 [Homo sapiens (human)] - Gene - NCBI".
8. (2012). "The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives". BMC.
9. (2014). "Fazio Londe syndrome: A treatable disorder". Annals of Indian Academy of Neurology.
10. Abdi, Mohammad. (2020). "Fazio-Londe Syndrome and Patient-centered Nursing Care: A Case Report". Client-Centered Nursing Care.
11. Poovazhagi Varadarajan, Vimal Thayanathi, and Leema C. Pauline. (2015). Fazio Londe syndrome: A treatable disorder. Ann Indian Acad Neurol, 18(1), 87-89
12. {{WhoNamedIt. synd. 1909
13. Londe, P. Paralysie bulbaire progressive, infantile et familiale. Rev. Med. 14: 212–254, 1894.