Compound Heterozygote Mutation in the SMPD1 Gene Leading to Nieman-Pick Disease Type A

Patient: Male, 11-month-old Final Diagnosis: Niemann-Pick disease type A Symptoms: Hepatosplenomegaly • failure to thrive • neurodegenerative disorder Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic OBJECTIVE: Rare disease BACKGROUND: Niemann-Pick disease (NPD) type A is an autosomal recessive lipid storage disorder caused by acid sphingomyelinase deficiency due to a mutation in the SMPD1 gene. Type A is the most severe phenotype of NPD, with early onset in infancy and unfavorable outcome in early childhood. CASE REPORT: An 11-month-old boy with hepatosplenomegaly, elevated liver transaminases, and faltering growth was admitted to our hospital for further assessment of potential liver disease. He had severe generalized muscular hypotonia, muscular hypotrophy, reduced muscular strenght, joint laxity, weak deep tendon reflexes, and severe motor developmental delay. Leukodystrophy was seen on the brain MRI, and brainstem auditory evoked potentials were characteristic for auditory neuropathy. A chest X-ray showed signs of interstitial lung disease, which was not further evaluated due to absence of respiratory distress. Liver biopsy histopathologic findings were indicative for lipid storage disease. Genetic analysis showed that the patient is a compound heterozygote in the SMPD1 gene – (NM_000543.5): c.573delT p.(Ser192Alafs*65), which was inherited from the mother and c.1267C>T p.(His423Tyr) was inherited from the father. Both variants were previously individually reported in NPD type A and B. The clinical phenotype in our patient was characteristic of NPD type A, with an early onset and a rapidly progresive neurodegeneration. The patient was included in multidisciplinary follow-up, providing him symptomatic treatment and support. CONCLUSIONS: We present a case of NPD type A caused by a rare compound heterozygote mutation in the SMPD1 gene. Most clinical findings and the disease course were typical for NPD type A, except for bilateral auditory neuropathy, which seems to be an uncommon finding in this phenotype and could be underestimated due to infrequent testing for auditory dysfunction.