Endocrine Abstracts

Background: Acid-labile subunit (ALS) protein plays a vital role in maintaining the serum IGF by prolonging the half-life of IGF/IGFBP binary complex. ALS deficiency due to IGFALS gene mutation results in primary IGF1 deficiency and associated with growth impairment, insulin resistance and occasionally delayed puberty.

Case report: A 9-year-old boy was referred for short stature (height −1.8 SDS and weight −1.8 SDS). He is the sixth of non-consanguineous parents of Asian origin. His birth weight was 2.9 kg (−1.3 SDS). His older sister (18 years) was diagnosed with idiopathic short stature with final adult height of −3.9 SDS. His mother measures 160 cm (−0.6 SDS) and father 174 cm (−0.6 SDS) and his mid-parental height 170.5 cm (−0.8 SDS). There was strong family history of type 2 diabetes. He later became overweight and had developed marked acanthosis nigricans. Pubertal assessment showed pubic hair Tanner stage 1, genital stage 2 testicular volume 6 ml bilaterally. Despite pubertal progression, his height velocity remained at 5.3 cm/year (−1.7 SDS).

Investigations for short stature showed persistently low IGF1 (<3.3 nmol/l, normal range 8.5–60), normal thyroid function. Insulin Tolerance test on two occasions failed to produce hypoglycaemia. Glucagon stimulation test showed normal GH peak (8 μg/l). Pubertal response was noted in LHRH test. Oral glucose tolerance test (OGTT) found to be normal with insulin resistance (HOMA-IR 19.9). Subsequent OGTT was impaired and whole exome sequence identified mutation in IGFALS gene.

Conclusion: ALS deficiency is a rare condition and it is associated with short stature and insulin resistance. Insulin insensitivity may be due to increased GH, impairing insulin action by lipolytic effect or by impairment of insulin signalling. Decreased IGF1 levels may also be playing a role in Insulin resistance. Despite the marked reduction in IGF1, the growth impairment can be moderate.