DGM (Dutch-German Mennonite)

Inheritance: autosomal recessive
Genes: ALMS 1

ALMS
ALSS

Rod-cone retinal dystrophy
Blindness
Sensorineural hearing loss
Obesity
Diabetes mellitus
Cardiomyopathy
Renal failure
Hepatic dysfunction
Hyperlipidemia
Hyperinsulinemia
Nystagmus

Alstrom Syndrome

Clinical Characteristics

General description (for patients): 

This rare disorder has a number of manifestations, including blindness, hearing loss, childhood obesity and diabetes.  Kidney, liver, heart and lung functions are also affected with chronic, progressive deterioration. Individuals can live to become adults but are unable to have children secondary to gonadal dysfunction.

Medical description: 

Alstrom’s syndrome is an inherited multisystem disorder in which ocular, renal, hepatic, pulmonary and endocrine functions are negatively impacted.  Childhood obesity, insulin-resistent diabetes mellitus (and sometimes insipidus), and dilated cardiomyopathy are common as well.  Longevity may extend into adult life but reproductivity is impaired secondary to hypogonadism.  Rod and cone dystrophy of the retina leads to variable degrees of blindness and a progressive sensorineural hearing loss occurs as well.  Most of these dysfunctions are progressive with onset later in the first decade and into the second.  Acanthosis nigricans has been reported.
Alstrom syndrome has some features in common with Bardet-Biedl syndrome but differs in lacking a clinically significant mental defect and polydactyly.

Genetics: 

This is a rare autosomal recessive disorder caused by a mutation in the ALMS1 gene on chromosome 2 (2q13). A single case has been reported among Canadian Mennonites.  The parents denied consanguinity but no pedigree has been reported.

Treatment: 

Indiviual therapies for specific organ dysfunction, such as hyperglycemia, jaundic, hearing aids, visual aids (early) and Braille, cardiac output dysfunction, and hyperlipidemia.

Prognosis: 

Individuals may live to adulthood but with blindness, deafness, obesity and diabetes.  Hypogonadism prevents reproduction.

Ancillary treatments and support: 

Dependent upon severity of systems involved.

Specialists and specialty centers: 

Neurologist, pediatrician, endocrinologist, nephrologist, cardiologist.

References:

Connolly, M.B., Jan, J.E., Couch, R.M., Wong, T.K.L., Dimmick, J.E., and Rigg, J.M.:  Hepatic dysfunction in Alstrom disease.  Am. J. Med. Genet. 40: 421-424, 1991.  PubMed ID: 1746604

Marshall, J.D., Hinman, E.G., Collin, G.B., Beck, S., Cerqueira, R., Maffei, P., Milan, G., Zhang, W., Wilson, D.E., Hearn, T., Tavares, P., Vettor, R., Veronese, C., Martin, M., So, W.V., Nishina, P.M., and Naggert, J.K.:  Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome.  Hum. Mutat. 28: 1114-1123, 2007.  PubMed ID: 17594715

Resources:

Alstrom Syndrome International

Associated Graphics