Differences in the clinical spectrum of two adolescent male patients with Alstrom syndrome

作者：Kuburovic Vladimir; Marshall Jan D^*; Collin Gayle B; Nykamp Keith; Kuburovic Nina; Milenkovic Tatjana; Rakic Sanja; Djuric Milena; Jecmenica Jovana; Milenkovic Svetislav; Naggert Juergen K

来源：Clinical Dysmorphology, 2013, 22(1): 7-12.

DOI：10.1097/MCD.0b013e32835b9017

• ALMS1
• Alstrom syndrome
• hypogonadotropic hypogonadism
• partial lipodystrophy
• tonic-clonic epilepsy

Alstrom syndrome is a rare disorder typified by early childhood obesity, neurosensory deficits, cardiomyopathy, progressive renal and hepatic dysfunction, and endocrinological features such as severe insulin resistance, type 2 diabetes, hyperlipidemia, and hypogonadism. Widespread fibrosis leads to multiple organ failure. Mutations in ALMS1 cause Alstrom syndrome. Two age-matched, unrelated adolescent males of Serbian descent with Alstrom syndrome underwent an extensive workup of blood chemistries, and ophthalmological, audiological, and genetic evaluations. Although both showed typical features of Alstrom syndrome in childhood, several differences were observed that have not been reported previously. Patient 1 was first studied at the age of 13 years for multisystemic disease and re-evaluated at the age of 15.5 years. Patient 2 is a 15-year-old boy who presented at birth with epilepsy and psychomotor developmental delay and generalized tonic-clonic seizures with severe cognitive impairment, features not documented previously in this syndrome. Sequencing analysis indicated two novel ALMS1 mutations in exon 8: p.E1055GfsX4 and p.T1386NfsX15. Metabolic and physiological similarities were observed in both patients, including severe insulin resistance, and truncal obesity with fat loss suggestive of partial lipodystrophy, supporting evidence for a role for ALMS1 in adipose tissue function. The unusual phenotypes of clonic-tonic seizures and severe cognitive abnormalities and lipodystrophy-like adiposity pattern have not been documented previously in Alstrom syndrome and may be an under-reported abnormality.

• 出版日期2013-1