Introducción:

LC-FAOD are rare, life-threatening, treatable autosomal-recessive conditions impairing energy production. LC-FAOD present clinically with hypoglycemia, cardiomyopathy, cardiac arrhythmias, retinopathy, and rhabdomyolysis. LC-FAOD can be detected at birth through acylcarnitine NBS and/or later via molecular diagnosis and/or acylcarnitine testing.

Metodología:

Patients in US/Canada/Mexico with clinical diagnosis/suspicion of LC-FAOD and an acylcarnitine test ordered were eligible for sponsored programs run at one of two laboratories in US or Brasil. Both panels include the 6 LC-FAOD genes (ACADVL, CPT1A, CPT2, HADHA, HADHB, SLC25A20) plus additional genes/disorders associated with abnormal acylcarnitines.

Resultado(s):

January 2024: 111/1,332 patients tested had ≥2P/LP/VUS LC-FAOD gene variants (MDx), 78 positive (≥2 P/LP) and 33 potential-positive (LP/VUS, P/VUS, VUS/VUS): 67% ACADVL, 16% CPT2, 10% HADHA, 3% HADHB, 3% SLC25A20, 1% CPT1A. Another 17 patients were heterozygous for variants in ≥2 LC-FAOD genes and 123 had one LC-FAOD variant; 87 had a non-LC-FAOD gene diagnosis. Patients with ≥2P/LP/VUS LC-FAOD gene variants were found in all age groups: 10.6% <1y, 2.5% 1y-12y, 7.2% 13y-20y, 13.5% 21y-40y, and 11.3% ≥40y. Eighty-four LC-FAOD MDx patients (n=111) reported abnormal NBS and 64 reported abnormal/inconclusive acylcarnitines. The 5 most frequently reported clinical signs in patients with >2P/LP/VUS LC-FAOD variants were elevated CK-63%, rhabdomyolysis-44%, myopathy-32%, cardiomyopathy-15%, and hypoglycemia-15%.

Conclusion(es):

LC-FAOD may be identified at birth but must be considered later in life also. Late diagnosis of LC-FAOD suggests patients were born before US NBS expansion in 2008 and that LC-FAOD are not readily identified at birth as they aren´t included in Mexico’s NBS program.