| Background: Ghosal hematodiaphyseal dysplasia (GHDD) is an rare autosomal recessive skeletal condition that is recognized by thickening of the diaphyseal bones and progressive bone marrow sway. Less than 40 cases have been reported globally, primarily from the Indian subcontinent. The condition is due to biallelic pathogenic variants in the TBXAS1 gene causing ineffective thromboxane A synthase. Mutations causing GHDD are known to strictly cause hematologic and skeletal abnormality, without an association to congenital heart disease. This is the first case that describes GHDD associated with an atrial septal defect (ASD). Case Presentation: A 17-month-old girl was brought in with severe failure to thrive and deformity of her left upper limb. Upon examination left radius bone was not there and growth parameters were below the 3rd centile. Wide and fixed split S2 with ejection systolic murmur was found on cardiac auscultation. Radiography shows enlarged heart, big pulmonary arteries and small bones. A large ostium secundum ASD with left to right shunt and right heart dilatation was seen in echocardiography. Hematologic test showed isolated thrombocytopenia with preservation of other cell lines. A pathogenic TBXAS1 mutation responsible for GHDD was identified in a patient suspected to have Holt–Oram syndrome. The child had successful surgical ASD patch closure, during which a left atrial membrane was discovered and removed. The post-op recovery was uncomplicated and the patient continues to be monitored for developing hematological involvement.