Farber disease and SMA-PME are both caused by mutations of only one gene : the ASAH1 gene — discovered in 1996¹ — which encodes the enzyme acid ceramidase, essential for normal cellular function.

Both conditions affect boys and girls equally. The ASAH1 gene is located on an autosome — a chromosome shared by both sexes — which means neither parent's sex influences transmission.

Both parents are healthy carriers: each carries one defective copy of the gene, but since the gene is recessive, a single defective copy is not enough to cause disease. However, when two carriers have a child, there is a 1-in-4 chance the child inherits both defective copies and develops the disease.

Both Farber disease and SMA-PME are lysosomal storage diseases. The defective ASAH1 gene prevents lysosomes — the cell's waste disposal/recycling system — from performing their essential function of breaking down cellular byproducts.

When both copies of the ASAH1 gene are defective, acid ceramidase — the enzyme normally responsible for processing ceramides (lipids found in cell membranes) — becomes severely non-functional. This leads to a toxic buildup of ceramides in most tissues, causing progressive multi-organ damage.

The degree of enzyme activity remaining determines which condition develops: near-total loss of function leads to Farber disease, while a partial deficiency (10–30% activity) results in SMA-PME — with a later onset and slower progression.