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Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in Polish patients: 2024 update
Patryk Lipiński1, Agnieszka Ługowska2, Anna Tylki-Szymańska3
1Institute of Clinical Sciences, Maria Skłodowska-Curie Medical Academy, Warsaw, Poland.
Insights
Acid sphingomyelinase deficiency (ASMD) is a progressive lysosomal storage disease in children. Early diagnosis in Polish patients revealed characteristic symptoms like enlarged spleen and liver, and altered lipid levels, aiding screening.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disease (LSD).
- It is caused by pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.
Purpose of the Study:
- To update the 2024 findings on chronic visceral and neurovisceral ASMD in Polish pediatric patients.
- To characterize the clinical and genetic profiles of ASMD in this cohort.
Main Methods:
- Systematic follow-up of pediatric patients (0-18 years) diagnosed with ASMD.
- Genetic analysis to identify SMPD1 gene variants.
- Biochemical assessment including lipid profiles and lyso-sphingomyelin (lyso-SM) levels.
Main Results:
- Seven pediatric patients were enrolled, including two newly diagnosed cases.
- Common findings included splenomegaly, mild hepatomegaly, decreased HDL-C, and elevated lyso-SM in dried blood spots (DBS).
- Seven SMPD1 variants were identified, with missense variants being most common (71%).
Conclusions:
- Pediatric ASMD is a slowly progressive disorder with key features: spleno-hepatomegaly, dyslipidemia (notably low HDL-C), and potential lung disease.
- Cherry-red spot can be present in both visceral and neurovisceral forms.
- Assessing acid sphingomyelinase activity and lyso-SM levels in DBS are recommended as primary screening methods for ASMD.
Background:
Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disease (LSD) associated with biallelic pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.
Objectives:
The aim of this study was to provide the 2024 update on chronic visceral and neurovisceral ASMD diagnosed in the infancy/childhood in Polish patients.
Material And Methods:
All the patients diagnosed in the pediatric age (0-18 years) with ASMD, both chronic neurovisceral and visceral type, and then systematically followed up, were enrolled into the study.
Results:
A total number of 7 patients were enrolled into the study. Four patients were previously reported. Two patients were newly recognized with ASMD - 1 with chronic visceral and 1 with chronic neurovisceral ASMD. Splenomegaly was noted in all the patients while a mild liver enlargement was observed in 4 of 7 patients. All patients presented with decreased high-density lipoprotein cholesterol (HDL-C) and decreased serum 25-hydroxy-vitamin D concentration while almost all (6 of 7) with hypercholesterolemia. Cherry-red spot was observed in 5 of 7 patients, including 1 patient with neurovisceral type. Seven various SMPD1 gene variants were identified and missense variants were the most common types of genetic lesions, comprising 71% of all alleles. In all the screened patients, lyso-sphingomyelin (lyso-SM) in dried blood spot (DBS) was found elevated; however, the greater values were observed for patients with chronic neurovisceral type.
Conclusion:
Chronic acid sphingomyelinase deficiency (ASMD) is a slowly progressive disease. Pediatric ASMD is characterized by spleno-hepatomegaly, dyslipidemia (with decreased HDL-C as the most characteristic) and infiltrative (interstitial) lung disease. Both visceral and neurovisceral chronic ASMD patients could present with cherry-red spot. Both acid spingomyelinase activity and lyso-spingomyelin concentration in DBS should be regarded as a first-tier screening method into ASMD.
