This study describes a diagnostic pitfall in the laboratory diagnosis of patients with
sphingomyelinase deficiency (SMD;
Niemann-Pick disease types A and B; NPA and
NPB), in cases where
sphingomyelinase activity was not determined with
sphingomyelin as the natural enzymic substrate. Four of 24 SMD patients studied had falsely normal or enhanced activity, when a so-called artificial
sphingomyelinase substrate, 2-N-(hexadecanoyl)-amino-4-nitrophenyl
phosphorylcholine (HNP), was used, whereas SMD was clear with the
sphingomyelin substrate. Those four patients had the Q292 K mutation of the
acid sphingomyelinase gene (SMPD1) on at least one allele. Three of the four patients (no data available from one) experienced only late-infantile or juvenile, though distinct, neurological involvement, where
learning disabilities, hypo- or areflexia or mild
ataxia were initial signs. The laboratory pitfall with HNP substrate, which is used in many laboratories, raises the risk that some SMD patients are overlooked, and it prevents the consideration of a late-manifesting neurological course in some patients as well as the planning of
enzyme substitution
therapy in non-neurological SMD (
NPB) patients. Since classical
NPB is very rare, it is suggested that SMD patients with late- or mild-manifesting neurological symptoms should better be assigned to additional SMD subgroups than grouped with
NPB.