sma differential diagnosis

A case report on a patient with lysosomal acid lipase deficiency (LAL-D) highlighted the importance of the accurate diagnosis of this rare disease. In this case, the patient was previously diagnosed with a glycogen storage disease (GSD) and wrongfully treated for at least 16 years.

The team of researchers led by Siuffi-Campo suggested that LAL-D is commonly underdiagnosed, explaining that “In most cases, a timely diagnosis is not made or this entity is not suspected due to lack of knowledge, and also to limited access to confirmatory diagnostic tests, which suggests that the real prevalence of the entity is higher.” The absence of prevalence studies in Latin America regarding LAL-D further contributes to this scenario. 

The case published in Hepatología studied a male patient who was initially treated with exogenous growth hormone due to failure to thrive as his only medical history. He later consulted at age 4 with hepatomegaly, transaminase elevation, and dyslipidemia. A liver biopsy was taken, reporting histopathological changes compatible with GSD, and treatment with cornstarch was initiated. Further checkups revealed clinical and laboratory improvement.

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It was not until 15 years later that genetic testing was performed. A chromosomal microarray (CMA) demonstrated deletions on chromosome 10 unrelated to GSD, and a year later, a multigene study incidentally revealed a homozygous genotype for the LIPA gene, which resulted in the lysosomal acid lipase enzyme deficit. Previous treatment was suspended, and the patient began receiving statins while a multidisciplinary team including nutritionists, hepatologists, and cardiologists performed routine evaluations.

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LAL-D can be caused by multiple mutations, yielding a wide range of symptoms and age of onset according to the severity of the enzyme deficit. In this patient, the enzyme activity was 31.1 mcmol/L/h for a reference value of >32.5 mcmol/L/h, corresponding to the mild to moderate symptoms observed. 

Moreover, treatment can range from statins and lifestyle changes to liver and hematopoietic transplants. Recombinant enzyme therapy was also recently studied with promising results, although its high cost limits its use.

Finally, although LAL-D remains a diagnostic challenge, some key features such as hepatomegaly have been found in 99% of the cases in children, and transaminase elevation may be an early sign of this disease.

“LAL-D should be suspected in the presence of persistent liver or lipid abnormalities, with no clear cause, in which case the determination of LAL activity and a subsequent confirmation diagnosis with molecular analysis of the LIPA gene would be indicated,” the authors suggested. 


Siuffi-Campo S, Londoño-García R, Espinosa-Herrera Y, Pérez-Cadavid J, Muñoz-Maya O. Lysosomal acid lipase deficiency, an underdiagnosed disease. Case report. Hepatología. 2022:97-105. doi:10.52784/27112330.151