Short stature due to primary acid-labile subunit deficiency

Short stature due to primary acid-labile subunit (ALS) deficiency, also known as ALS deficiency or IGFALS deficiency, is a rare genetic growth disorder caused by mutations in the IGFALS gene. The acid-labile subunit is a protein produced primarily in the liver that plays a critical role in stabilizing insulin-like growth factor 1 (IGF-1) and its principal binding protein (IGFBP-3) in the bloodstream by forming a ternary complex. Without functional ALS, IGF-1 and IGFBP-3 are rapidly cleared from the circulation, resulting in markedly reduced serum levels of both proteins despite normal or even elevated growth hormone secretion. The primary clinical feature is mild to moderate short stature, typically becoming apparent during childhood. Affected individuals usually present with height below the normal range but the degree of growth impairment is often less severe than in other forms of growth hormone/IGF-1 axis deficiency. Additional features may include delayed puberty and insulin insensitivity. Bone age may be mildly delayed. Notably, despite very low circulating IGF-1 and IGFBP-3 levels, the clinical phenotype is relatively mild, suggesting that locally produced IGF-1 partially compensates for the reduced circulating levels. Treatment options are limited. Growth hormone therapy has been attempted in some patients but generally shows a poor or modest response, likely because the fundamental problem is the inability to maintain stable circulating IGF-1 levels rather than growth hormone deficiency itself. Recombinant IGF-1 therapy has been considered but evidence for its efficacy in this specific condition remains limited. Management is primarily supportive, with monitoring of growth and pubertal development. Genetic counseling is recommended for affected families.

Common questions about Short stature due to primary acid-labile subunit deficiency