title: Differences in the clinical spectrum of two adolescent male patients with Alström syndrome.
abstract: Alström 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 Alström syndrome. Two age-matched, unrelated adolescent males of Serbian descent with Alström syndrome underwent an extensive workup of blood chemistries, and ophthalmological, audiological, and genetic evaluations. Although both showed typical features of Alström 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 Alström syndrome and may be an under-reported abnormality.
authors.affiliation: Mother and Child Healthcare Institute of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kuburović
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.forename: Keith
authors.initials: K
authors.lastname: Nykamp
authors.forename: Nina
authors.initials: N
authors.lastname: Kuburović
authors.forename: Tatjana
authors.initials: T
authors.lastname: Milenković
authors.forename: Sanja
authors.initials: S
authors.lastname: Rakić
authors.forename: Milena
authors.initials: M
authors.lastname: Djuric
authors.forename: Jovana
authors.initials: J
authors.lastname: Ječmenica
authors.forename: Svetislav
authors.initials: S
authors.lastname: Milenković
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D056769:Alstrom Syndrome / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D003072:Cognition Disorders / Q000235:genetics; D004252:DNA Mutational Analysis; D057210:Delayed Diagnosis; D050171:Dyslipidemias / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007333:Insulin Resistance; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D012640:Seizures / Q000235:genetics; D055771:Serbia
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins