Coexistence of Niemann-Pick type A and patent ductus arteriosus in an infant: An unusual clinical case

INTRODUCTION

Niemann–Pick disease represents a heterogeneous group of inherited metabolic conditions characterised by intracellular accumulation of lipids. Types A and B arise from mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM), the lysosomal enzyme responsible for hydrolysis of sphingomyelin into ceramide and phosphocholine.^[1] Loss of enzymatic activity results in progressive deposition of sphingomyelin within cells of the reticuloendothelial system and several parenchymal organs.

The infantile form (type A) manifests within the first months of life and is marked by neurodevelopmental regression, organomegaly and failure to thrive. Rapid neurological decline typically leads to death in early childhood.^[2-3] ASM activity is significantly reduced or absent, resulting in hepatosplenomegaly, failure to thrive, hypotonia, and rapid neurodegeneration, with the majority of affected children dying by early childhood.^[4-5] In contrast, type B predominantly affects visceral organs and spares the central nervous system, while type C involves abnormal intracellular cholesterol trafficking rather than sphingomyelinase deficiency.

The combined incidence of types A and B is approximately 1 in 250,000 live births, although prevalence varies among specific populations. Ophthalmic findings, especially macular cherry-red spots, reflect lipid accumulation in retinal ganglion cells and may provide an early diagnostic clue.^[6] Structural cardiac abnormalities are not considered a recognised component of this disorder. We describe an infant with genetically confirmed Niemann–Pick disease type A in whom patent ductus arteriosus (PDA) was detected during evaluation of respiratory symptoms.

CASE REPORT

A seven-month-old male infant presented to the paediatric outpatient department with cough and cold and was treated for bronchiolitis. Because of recurrent respiratory episodes, echocardiography was performed, which demonstrated a small PDA measuring 2.4 mm [Figure 1].

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Figure 1:

Echocardiogram of the patient showing a small patent ductus arteriosus of 2.4mm.

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General examination revealed coarse facial appearance, protruding tongue, hepatosplenomegaly and delayed developmental milestones [Figures 2-3]. These findings suggested an underlying metabolic disorder, particularly a lysosomal storage disease. Ophthalmologic examination showed bilateral cherry-red spots. Laboratory investigations demonstrated mild thrombocytopenia (platelet count 90,000/mm3) and mild hypercholesterolemia (220 mg/dL), with other parameters within normal limits.

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Figure 2:

Clinical image of the patient shows coarse facial features and hepatosplenomegaly.

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Figure 3:

Clinical image showing coarse facial features and a depressed nasal bridge.

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Targeted genetic sequencing identified a homozygous nonsense mutation in exon 1 of the SMPD1 gene (chr11: g.6390855G>A; depth 94×), producing premature truncation at codon 86 (p.Trp86Ter) [Figure 4]. The child was managed symptomatically, and regular follow-up was advised.

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Figure 4:

Shows the findings of targeted gene sequencing.

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DISCUSSION

Niemann–Pick disease types A and B are caused by pathogenic variants affecting ASM activity, leading to lysosomal lipid accumulation in the liver, spleen, lungs, bone marrow and nervous system. Disease severity depends largely on residual enzyme function, explaining the aggressive course observed in type A patients.

PDA is a congenital persistence of the fetal vascular connection between the aorta and pulmonary artery.^[7] Although frequently encountered in premature infants, it is uncommon in full-term neonates and may occur in association with genetic syndromes or environmental influences.^[8] Cardiac structural defects are not classically described in Niemann–Pick disease.

Certain lysosomal storage disorders, such as Pompe and Fabry disease, demonstrate cardiovascular involvement, typically presenting as cardiomyopathy or conduction abnormalities. However, a direct link between ASM deficiency and congenital cardiac malformations has not been established. In the present case, the presence of PDA most likely represents a coincidental finding rather than a manifestation of the metabolic defect. Nevertheless, recognition of additional anomalies in such patients is clinically relevant because they may influence treatment decisions and prognosis.

Currently, therapy for type A disease remains supportive. Genetic counselling is essential due to autosomal recessive inheritance and the availability of carrier detection and prenatal testing.^[9]

CONCLUSION

Niemann–Pick disease type A is a severe, early-onset lysosomal storage disorder characterised by progressive neurovisceral involvement. Diagnosis relies on clinical suspicion supported by ophthalmologic features and confirmed by molecular testing. Detection of PDA in this patient appears incidental but expands the spectrum of associations reported with the disease and underscores the need for multidisciplinary evaluation, such as appropriate counselling and supportive care.