Categories: Homeostasis / metabolism phene , Endocrine / exocrine gland phene (incl mammary gland) , Liver/biliary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 246650 (trait) , 611761 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2025

Species-specific name: Hypertriglyceridemia-induced pancreatitis

Species-specific symbol: HIP

Molecular basis: The LMF1 gene encodes lipase maturation factor 1, a transmembrane protein in the endoplasmic reticulum required for the correct posttranslational maturation of the enzymes lipoprotein lipase (LPL) and hepatic lipase (HPL). Loss-of-function of LMF1 results in severe primary hypertriglyceridemia, which may trigger episodes of acute pancreatitis (Alves et al. 2024).
Drögemüller et al. (2025): "Whole genome sequencing of an affected foal identified a homozygous loss of function variant in LMF1 encoding lipase maturation factor 1 [omia.variant:1823]. The variant, XM_023616679.1:c.369_373delinsTCT, leads to an early frameshift and is predicted to alter or truncate 78% of the LMF1 coding sequence. [The authors] genotyped the variant in a cohort of 2122 FM horses and identified 11 homozygous mutant animals including all eight foals that had initially been identified based on their clinical presentation. [All] homozygous mutant animals had a comparable phenotype and were inbred to the same stallion."

Clinical features: The main diagnostic feature of affected animals are severely elevated plasma triglyceride levels above 10 mmol/l compared to the reference range of 0.6-1 mmol/l for foals and 0.17-0.59 mmol/l for adult horses (Drögemüller et al. 2025). 
Drögemüller et al. (2025) reported 11 affected Franches-Montagnes horses: "Ten of the 11 affected horses died or were euthanized between 6 days and 3 months of age due to severe pancreatitis. The most common clinical signs in affected foals included apathy, reluctance to nurse, abdominal distension and diarrhea, with fever observed in some cases. Other common clinicopathological abnormalities in foals included hypoproteinemia, azotemia, hyperbilirubinemia, hyperlipasemia, and elevated serum amyloid A concentrations. ... One affected horse, a 13 year-old gelding, survived until adulthood and presented with a history of chronic weight loss, diarrhea, and intermittent fever, which had acutely worsened. ... The horse was humanely euthanized after several days of treatment due to its lengthy medical history and compromised quality of life."

Pathology: Drögemüller et al. (2025): "Pathological examinations in eight affected foals revealed severe, acute to chronic necrotizing pancreatitis and extensive fibronecrotizing peritonitis. The affected adult horse was diagnosed with severe, multifocal, chronic active cholangiohepatitis and acute necrotizing hepatitis, mild chronic pancreatic fibrosis, and mild multifocal chronic peritoneal fibrosis."

Prevalence: Drögemüller et al. (2025) reported a 15% carrier frequency for omia.variant:1823 in 2111 unaffected Franches-Montagnes horses at the time of variant discovery.  

Breed: Freiberger (Horse) (VBO_0000965).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: