ABHD4 and Anorexia Nervosa

The association between ABHD4 (HGNC:20154) and anorexia nervosa (MONDO:0005351) has been recently explored in candidate gene studies. In one study using a targeted gene panel of 163 genes in 135 Italian patients diagnosed based on DSM‐V criteria (PMID:38112957), ABHD4 was identified among 16 candidate genes potentially contributing to the genetic architecture of anorexia nervosa. Although the analysis involved a moderately sized cohort, detailed variant-level data and clear familial segregation information remain limited.

Genetic evidence for ABHD4 in anorexia nervosa is derived from observations of rare variants in case reports and multi‐patient studies. The inheritance mode has been presumed to be autosomal recessive given the complexity of the trait, but no definitive segregation data (e.g. affected relatives) have been reported (PMID:38112957). This leaves the precise contribution of individual alleles and their pathogenic mechanisms somewhat ambiguous.

No specific HGVS‐formatted variant has been reported for ABHD4 in the context of anorexia nervosa, which further limits detailed interpretation at the sequence level. As a result, the genetic evidence is based on the overall candidate gene approach rather than on the demonstration of a recurrent, deleterious mutation of the form “c.xxx (p.xxx)” in affected individuals.

In contrast to the genetic findings, functional evidence for ABHD4 has primarily been derived from studies examining its paralog activities in lipolysis regulation. One study investigating lipase activation provided insights into ABHD protein family functions (PMID:28211464), yet these experiments were conducted in a metabolic context (Dorfman-Chanarin disease) and do not directly address the mechanisms underlying anorexia nervosa.

Overall, the available data linking ABHD4 to anorexia nervosa remain limited. The absence of robust segregation analysis, detailed variant-level descriptions, and functional studies specific to anorexia nervosa restricts the clinical validity of the association. However, the inclusion of ABHD4 in multi‐gene panels suggests that it may contribute to the disease risk in a subset of patients, highlighting the potential for future research to clarify its role.

Key take‑home sentence: Although ABHD4 is emerging as a candidate gene for anorexia nervosa, further investigations including segregation analyses and targeted functional studies are needed to establish its clinical utility in diagnostic decision‑making.

References

• European review for medical and pharmacological sciences • 2023 • Genetic variants identified in novel candidate genes for anorexia nervosa and analysis of molecular pathways for diagnostic applications PMID:38112957
• Scientific Reports • 2017 • Molecular Basis of ABHD5 Lipolysis Activation PMID:28211464

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