Lysosomal acid lipase deficiency (LALD) is a rare autosomal recessive metabolic disorder. Mutations in the LIPA gene that encodes LAL result in disrupted triglyceride metabolism. Presentations and severity of the disorder are diverse and are often non-specific. Characterisations of LALD include dyslipidaemia and abnormal liver function which can overlap with conditions such as familial hypercholesterolaemia and non-alcoholic fatty liver disease (NAFLD). The rarity of LALD may mean that the condition is unrecognised or misdiagnosed. The development of effective enzyme replacement therapy for LALD has provided motivation for identifying the condition clinically. Diagnosis of LALD by genetic testing is costly. However the relatively inexpensive assay of LAL activity in dried blood spot (DBS) has made the diagnosis of LALD in clinical practice more available. We studied LALD screening in 3 cohorts: patients from hospital Lipid and Diabetes Clinics selected using the current recommended criteria,1 patients from hospital Liver Clinic who either had histological features in their liver biopsies that were consistent with LALD or who had diagnoses of non-alcoholic steatohepatitis (NASH), NAFLD or cryptogenic cirrhosis, and genetic testing for patients found to have reduced LAL activity to detect LALD carriers.
Eligible patients were consented for LALD screening. A single sample of blood was obtained either from a finger prick or from a venous blood sample. The blood was transferred to a DBS filter paper for processing. LAL activity <0.03 nmol/punch/h was diagnostic of LALD.
Patients with reduced LAL activity were offered genetic testing. Consenting patients gave a venous blood sample of 3ml.
1730 patients were screened for LALD from 8 centres in the UK. None of the patients in the cohort tested positive for LALD. 27 patients consented to have genetic testing. No abnormalities were detected. 100 patients in the Liver cohort were screened for LALD and none was positive for LALD.
Using the eligibility criteria we adopted, the detection rate of LALD was meagre. In our cohorts, we did not identify any patient with undiagnosed LALD in hospital Lipid, Diabetes or Liver clinics.