Discussion

Generalised arterial calcification of infancy, an autosomal recessive disorder, is characterised by abnormal calcification of medium and large-sized arteries, ^{Reference Bolster, Ali, Southall and Fowler2} leading to significant myointimal proliferation and arterial stenosis. Its prognosis is poor, with approximately 85% of affected infants succumbing within the first six months of life, often due to cardiovascular complications and heart failure. Diagnosis poses challenges due to the variability of clinical presentation and the rarity of the disease. ^{Reference Bolster, Ali, Southall and Fowler2} During the antenatal period, ultrasonography may reveal arterial calcification, foetal distress, and nonimmune hydrops as well as pleural and pericardial effusion. In infancy, patients frequently exhibit non-specific symptoms, including lethargy, vomiting, irritability, and shock, with peripheral pulses often being weak or absent. ^{Reference Bolster, Ali, Southall and Fowler2,Reference Chong and Hutchins3} Our patient presented with poor general condition, malnutrition, and fatigue upon admission.

Diagnostic imaging techniques, such as echocardiography, angiography, and tomography, play crucial roles in confirming the diagnosis. ^{Reference Pao, DeAngelis, Lovell, McIlhenny and Hagspiel4} Mutations in the ectonucleotide pyrophosphatase phosphodiesterase 1 gene, located on chromosome 6, are detected in 75% of patients (generalised arterial calcification of infancy 1). ^{Reference Rutsch, Ruf and Vaingankar5} Defects in the ectonucleotide pyrophosphatase phosphodiesterase 1 gene lead to a reduction in the level of inorganic pyrophosphate, which serves as a potent inhibitor of hydroxyapatite crystal deposition in vessel walls. The decrease in inorganic pyrophosphate levels results in the interruption of the normally eosinophilic internal elastic lamina by basophilic granules and calcium salts. In advanced stages, the internal elastic lamina is completely destroyed, and wide calcium bands become evident. Subsequent calcium deposition progresses to the media layer, leading to severe stenosis in the vascular lumen. ^{Reference Federici, Torii and Ciuffreda6} In some patients (generalised arterial calcification of infancy 2), mutations in the adenosine triphosphate binding cassette transporter C6 (ABCC6) gene are detected. ABCC6, a protein-coding gene, belongs to the superfamily of adenosine triphosphate binding cassette transporters. These proteins facilitate the transport of various molecules across extra- and intracellular membranes. Mutations in the ABCC6 gene are known to cause pseudoxanthoma elasticum. ^{Reference Rutsch, Ruf and Vaingankar5} Our patient tested positive for an ABCC6 gene mutation.

Bisphosphonates, synthetic analogues of inorganic pyrophosphate, have demonstrated a significant increase in survival rates. Studies have shown that treatment with bisphosphonates for four months to two years results in substantial regression of arterial and periarticular calcifications as confirmed by control tomography and ultrasonography. Moreover, recurrence of calcifications is unlikely unless treatment is discontinued. ^{Reference van der Sluis, Boot, Vernooij, Meradji and Kroon7} In the case of a child diagnosed with generalised arterial calcification of infancy undergoing heart transplantation, follow-up after a two-year bisphosphonate treatment revealed no involvement of coronary arteries. ^{Reference Giovannoni, Callea and Travaglini8} However, despite a preliminary diagnosis of generalised arterial calcification of infancy, our patient was unable to receive bisphosphonate treatment due to uncertainty regarding the diagnosis.

Burosumab is an Food and Drug Administration-approved anti-fibroblast growth factor 23 monoclonal antibody for the treatment of X-linked hypophosphataemia and tumour-induced osteomalacia. Although it is believed to be potentially beneficial in the treatment of generalised arterial calcification of infancy, it may increase ectopic calcification by reducing pyrophosphate levels, so its use in generalised arterial calcification of infancy treatment is controversial. ^{Reference Ziegler, Gahl and Ferreira9} In a patient initially diagnosed with X-linked hypophosphataemia, started on burosumab treatment and later found to have ectonucleotide pyrophosphatase phosphodiesterase 1-dependent rickets, no new calcifications developed over several months. ^{Reference Boyce, Gafni and Ferreira10}