Acid sphingomyelinase deficiency: The clinical spectrum of 2 patients who carry the Q294K mutation and diagnostic challenges

Mol Genet Metab Rep. 2022 Jul 19;32:100900. doi: 10.1016/j.ymgmr.2022.100900.

PMID: 36046391

Ulrike Blümlein, Eugen Mengel, Yasmina Amraoui

Highlights: Two case studies are presented, which illustrate the spectrum of disease in patients with a compound heterozygous Q294K pathogenic variant and the impact of false normal ASM activity results.

Abstract

Background: Pathogenic mutations in the SMPD1 gene are the cause of acid sphingomyelinase deficiency (ASMD). Specialist care is urgently needed for this fatal, chronic, and progressive condition. If individuals with the Q294K mutation undergo enzyme activity tests using synthetic fluorometric substrates, the diagnosis of ASMD may be postponed or missed.

Objective: The impact of false normal ASM activity results as well as the spectrum of disease in patients with a compound heterozygous Q294K pathogenic variant are shown in two case studies.

Keywords: Acid sphingomyelinase deficiency type A/B, HMU-PC, 6-hexadecanoylamino-4-methylumbelliferylphosphorylcholine, HNP, 2-N-(hexadecanoyl)-amino-4-nitrophenyl phosphorylcholine