Table 5.

Treatment of Manifestations in Individuals with GACI

Manifestation/
Concern
TreatmentConsiderations/Other
Arterial
calcification
Bisphosphonate therapy 1 using one of the following:
  • Etidronate (20 mg/kg/d PO)
  • Pamidronate (0.25 mg/kg on day 1, then 0.5 mg/kg/d on days 2 & 3 for 1st cycle, then 0.5 mg/kg/d x3 days IV per cycle; cycles rptd every 2 mos)
  • Risedronate (1mg/kg/wk PO)
  • After initiation of therapy, vascular calcifications have been reported to disappear as early as 2.5 wks (as assessed by radiographs) and as late as 2 yrs [van der Sluis et al 2006, Meradji et al 1978]
  • Vascular calcifications do not reappear after discontinuation of treatment even after 10 yrs [van der Sluis et al 2006]
  • Prolonged etidronate use in persons w/GACI has been assoc w/severe skeletal toxicity, incl radiographic findings resembling hypophosphatasia 2 or osteopetrosis 3 [Otero et al 2013]. Thus, some authors recommend close monitoring for resolution of arterial calcifications during treatment so that use of bisphosphonates can be discontinued as soon as possible [Otero et al 2013].
Hypertension Standard therapySince hypertension in GACI is likely caused by renal artery stenosis, it may be beneficial to use ACE inhibitors or angiotensin II type 1 receptor blockers.
Severe coronary
stenosis
Aspirin therapy if coronary stenosis is present
PXE retinal
changes
Intravitreal VEGF inhibitors for choroidal neovascularization
Hypophosphatemic
rickets
Calcitriol (15-25 ng/kg/d) & oral phosphate supplement (25-50 mg/kg/d in 3-5 daily doses)Doses adjusted based on alkaline phosphatase, PTH, & calciuria levels
Orthopedics eval if bone deformities developSurgical interventions may be necessary.
Hearing loss Hearing aids as indicated

ACE = angiotensin-converting enzyme; PTH = parathyroid hormone; VEGF = vascular endothelial growth factor

1.

It remains unclear whether bisphosphonates (etidronate in particular) are associated with improved survival.

2.

Radiographic findings resembling hypophosphatasia include pan craniosynostosis, bowing of long bones, metaphyseal cupping and fraying, and radiolucent tongues.

3.

Radiographic findings resembling osteopetrosis include osteosclerosis and femoral Erlenmeyer flask deformity.

From: Generalized Arterial Calcification of Infancy

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