Growth and Endocrinological Evaluation in Autosomal Recessive Proximal Spinal Muscular Atrophies Type I–III

Aims: Autosomal recessive proximal spinal muscular atrophies (SMA) are hereditary monogenetic disorders characterized by a ubiquitous deficiency of the survival of motor neuron protein in every cell, leading to a multisystemic disorder which mostly affects α-motorneurons for unexplained reasons. Clinical evaluation often shows hirsutism and early occurrence of pubic hair which was not observed in other neuromuscular disorders so that it is unclear whether this belongs to the multisystemic origin of the SMA. Actually, there are no data available concerning growth and pubertal development in patients with SMA I–III.

Methods: In a period of 18 months, 43 patients (21 females and22 males), 0.6 to 21.8 year's old with SMA type I–III (8 SMA I; 22 SMA II; and 13 SMA III) have visited our neuromuscular center for medical follow-up. Because of hirsutism and early occurrence of pubic hair, we designed a study to measure auxological and endocrinological parameters to determine the hypothalamus pituitary gland–gonad axis and the parameters of the adrenal gland. The key aspects are the evaluation of auxology and endocrinological abnormalities.

Results: Despite a high number of patients (32.6%) with extreme underweight, 20% of patients with SMA I–III have increased abdominal fat tissue easily measured by waist-to-hip ratio (WHR), especially in nonambulant patients.

Hirsutism is quite common (8/21), elevated testosterone or its metabolites were found in five of eight patients. An association with overweight or increased WHR could not be found. Of the eight patients, four patients aged 4 to 8.5 years showed a premature pubarche as a sign for an early maturation/activation of the adrenal gland. A significant disturbance of hormones or any association to overweight could not be found.

Conclusion: Increased abdominal fat tissue, hirsutism, and premature pubarche frequently seen in SMA I–III patients are risk factors for developing a metabolic syndrome. The clinical relevance of this data for patients requires further studies.

Medical follow-up of SMA I–III patients from childhood up to adulthood should take this into account.

Keywords: spinal muscular atrophy, hirsutism, premature pubarche.