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Identification and Diagnostic Protocol for Suspected Acid Sphingomyelinase Deficiency in a Medical Genetics Service in São Paulo

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical- Pediatric
  • Secondary Categories:
    • Clinical- Pediatric
Introduction:
Niemann-Pick disease is a rare genetic disorder resulting from mutations in the sphingomyelin phosphodiesterase 1 gene, which leads to acid sphingomyelinase deficiency (ASMD) and the intracellular accumulation of sphingomyelin. Reliable estimates of ASMD incidence worldwide are currently lacking. Although some estimates based on actual diagnoses place the incidence of ASMD at approximately 0.5 per 100,000 births. Early and accurate diagnosis is crucial for effective management and treatment. This study aimed to refine the identification and diagnostic protocol for ASMD within a Medical Genetics Service in São Paulo

Methods:
We reviewed our database for suggestive findings of ASMD, from the last 20 years. We cross-referenced data including bone marrow aspirate findings with sea-blue histiocytes, cases of hepatosplenomegaly, hematological abnormalities such as thrombocytopenia, and lipid profile alterations. 

Results:
We systematically analyzed 13,000 family records to identify relevant clinical and laboratory findings. Following a thorough review of medical records, we identified 23 patients with potential ASMD-related clinical manifestations and scheduled consultations for further evaluation. We conducted comprehensive clinical assessments for 11 patients. Of these, 3 patients were confirmed to have ASMD. The confirmed cases included a 52-year-old female, a 16-year-old female, and her 19-year-old brother. These patients have been provided with ongoing clinical follow-up, genetic counseling, and are being considered for enzyme replacement therapy. Accurate ASMD incidences are challenging due to the inherent risk of underdiagnosis. This often relies on limited awareness of the disease among healthcare providers and the broad spectrum of its clinical manifestations, which can lead to delays in diagnosis.ASMD, a rare genetic disorder, presents with varied symptoms including hepatosplenomegaly, hematological abnormalities, and lipid profile alterations, which can be easily mistaken for more common conditions. Consequently, the journey from initial symptom presentation to definitive diagnosis can be protracted, often spanning several years and involving multiple specialist consultations.The protocol described in this study represents a significant advancement in the identification and diagnostic process for ASMD. By systematically reviewing 20 years of historical data, we were able to leverage a wealth of clinical and laboratory information to identify potential cases. The use of targeted clinical evaluations, including cross-referencing bone marrow aspirate findings with the presence of sea-blue histiocytes and assessing for common ASMD-related manifestations such as hepatosplenomegaly and thrombocytopenia, has proven effective in enhancing diagnostic accuracy.

Conclusion:
However, despite the success of this protocol, there are areas that warrant further attention. For instance, continuous awareness and education about ASMD among healthcare professionals are crucial to minimize diagnostic delays and ensure timely referral to specialized genetic services. Additionally, expanding the protocol to include broader genetic testing and further research into the disease’s natural history and progression could enhance diagnostic accuracy and therapeutic outcomes. This protocol demonstrates an effective approach to identifying and diagnosing ASMD in a large cohort by leveraging historical data and targeted clinical evaluations. The implementation of this protocol has led to the successful diagnosis and management planning for patients, highlighting the importance of systematic data review and interdisciplinary collaboration in rare disease diagnosis

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