A new mutation found in the LIPA gene was associated with lysosomal acid lipase deficiency (LAL-D), as published in Research Square. The mutation detected in exon 4: NM_001127605: c.G353A (p.G118D) represents glycine substitution with aspartic acid and allowed an accurate recognition of LAL-D in a patient previously diagnosed with hemophagocytic lymphohistiocytosis (HLH).

“Considering the similarities in presentation of WD [Wolman disease] and HLH, the patient’s life can be saved if special attention is paid to presenting features of a patient with suspected HLH, i.e., symptoms, findings on physical exams, laboratory values, and radiologic findings, and the proper treatment is urgently initiated,” the authors wrote.

Reporting the novel mutations of WD can help geneticists interpret the results of their patients’ genetic studies appropriately, leading to correct diagnosis and treatment.”


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This finding was recently reported in a case study of a 4.5-month-old male brought to the hospital after experiencing a fever of 2 weeks of duration after vaccination and jaundice and drowsiness for 5 days. Although no other symptoms were initially reported, the parents noticed abdominal distension since birth and a weight loss of 500 g in the past 2 weeks.

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Birth and family history was noncontributory. Findings in the physical examination included pale and icteric skin, ill appearance, mild respiratory distress, and a severely distended abdomen with enlarged liver and spleen. Laboratories ran after admission reported anemia, direct hyperbilirubinemia, low albumin, elevated liver enzymes, and ferritin, the rest of the values were normal.

Viral blood cultures were negative, and echocardiography, renal artery sonography, and bone marrow aspiration were normal. Due to these findings, HLH was diagnosed, and treatment with cyclosporine, dexamethasone, and methylprednisolone was initiated.

The patient died 17 days after admission due to cardiopulmonary collapse secondary to hepatic failure, and the genetic analysis came positive for the novel LIPA gene mutation after the patient passed away and further revealed the heterozygous status of the parents.

The authors mention 13 other cases of LAL-D with similar presentations; some were also misdiagnosed with HLH until postmortem findings. All patients died in less than 2 months from initial evaluation except 1 case where the outcome is not specified. In most cases, consanguinity was present, and physical examination and laboratory findings were consistent with slight variations. 

The pathophysiology of WD is known to showcase the absence of functional lysosomal acid lipase (LAL) due to mutations in the LIPA gene. Moreover, 2 phenotypes leading to scarce or absent LAL activity have already been recognized, but no previous report was linked to the mutation detected in this case.

“Only Glycine is flexible enough to make these torsion angles, and mutation into another residue will force the local backbone to change into an incorrect conformation, which will disturb the local structure and impair the protein’s function,” the authors concluded.

Reference

Ashari K, Azari-Yam A, Shahrooei M, Ziaee V. Wolman disease presenting with HLH syndrome and a novel LIPA gene variant: a case-based review. Res Sq. Published online January 20, 2022. doi:10.21203/rs.3.rs-1203156/v1