Farber Lipogranulomatosis With Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy: Expanding the Phenotypic Spectrum

Background Farber lipogranulomatosis with spinal muscular atrophy with progressive myoclonic epilepsy (FL-SMA-PME) is inherited in an autosomal recessive manner because of pathogenic variations in the ASAH1 gene. We report a series of 4 children from 3 different families with genetically proven FL-SMA-PME. Cases A 5-year-old girl born of a second-degree consanguineous marriage presented with progressive myoclonic epilepsy for 4 years, neuroregression, and skeletal deformities. A 6-year-old girl born of a non-consanguineous marriage presented with milestones regression, cognitive decline, myoclonic jerks, and joint pain from the age of 2 years. Her elder sibling had similar complaints. A 3-year-old girl born to second-degree consanguineously married parents presented with developmental delay and myoclonic jerks. The common features noted were frontal bossing, central hypotonia, contractures, and flexion deformity of the wrist and fingers, flat feet with flexion deformity and contractures, fasciculations, generalized osteopenia, and swelling at multiple joints. Results All 4 children had developmental regression and PME. Central hypotonia was noted in 4 of 4 children (100%). Three of 4 children (75%) had corneal clouding, 2 of 4 (50%) had nystagmus, and 2 of 4 (50%) had cherry-red spots. Nerve conduction study showed axonal motor type polyneuropathy in 4 of 4 patients (100%). Genetic testing in patient 1 revealed c.553T>C(p.Trp185Arg) in exon 8, patients 2 and 3 revealed c.553T>C(p.Trp185Arg) in exon 8 and deletion c.(126+1_127-1)_(351+1_352-1) in exons 2 to 4, and patient 4 revealed c.505T>C(p.Trp169Arg) in exon 8 and c.314T>C(p.Leu105Pro) in exon 5 of ASAH1 gene. Conclusion ASAH1- related disorders are multifaceted, representing an amalgamation of storage disorder, neurodegeneration, and peripheral nervous system involvement. Misdiagnosis can be common because of the multitude of presentations.