Report of Five Italian Alström Patients

V. Munno & M. Imi, P.Maffei, J.D. Marshall, G. Collin, C. Scandellari, N.Sicolo.

Department of Medical and Surgical Sciences, Clinica Medica 3^, University School of Medicine, Padua, Italy; The Jackson Laboratory, Bar Harbor, ME, USA.

The Alström syndrome (ALMS) is a rare autosomal recessive disorder characterized by retinal degeneration, childhood obesity, progressive hearing impairment, hyperinsulinemia, non-insulin-dipendent diabetes mellitus and kidney and heart failure. Mental retardation is absent and the extremities are normal. Other metabolic and endocrinological abnormalities have been described: hypothyroidism, hypogonadism, diabetes insipidus, growth hormone deficiency, hyperuricemia and hyperlipidemia. Manifestations observed in some Alström syndrome patients include acanthosis nigricans, short stature, scoliosis, kiphosis, hyperostotis frontalis interna, muscle dystonia, advanced bone age and subcapsular cataract. In the final stages of the disease, affected individuals exhibit progressive chronic nephropathy with eventual kidney failure. The most frequent causes of death include hepatic dysfunction and congestive heart failure secondary to dilated cardiomyopathy. The ALMS involves multiple organ system with a complex interaction between pathways; phenotypic expression varies considerably, even within sibships. The ALMS is caused by the mutation of a single gene, trasmitted as an autosomal recessive characteristic. Alström syndrome gene (ALMS1) located in the short arm of chromosome 2, has been recently cloned but the product and function of the gene is unknown.

Despite the rarity of this sindrome, five patients with ALMS, three males and two females, belonging to four different Italian families (two patients are siblings) and with ages ranging from 13 to 33 years, have been evaluated in our Center. In december 2001, a 14-year-old patient we had in treatment dead of complications related to an ALMS-associated dilated cardiomyopathy. Genetic analysis for all patients and their families conducted at the Jackson Laboratory in Bar Harbor (Maine, USA) confirmed linkage to chromosome 2p13 or mutation in ALMS. The characteristics of the five patients reported in Tab 1.

Although difficulty of arriving at a correct early diagnosis of the ALMS, for the extreme rarity of the disease and variability in its manifestations, the precocious identification of the ALMS is necessary for an adequate treatment and for preventing typical complications of this disease responsible of the precocius damage of the vital organs like kidney and liver.

Tab 1: Characteristies of the case histories we observed

	P1	P2	P3	P4	P5
Nystagmus	Yes	Yes	Yes	Yes	Yes
Photophobia	Yes	Yes	Yes	Yes	Yes
Progressive retinal dystrophy	Yes	Yes	Yes	Yes	Yes
Sensorineural hearig loss	Yes	Yes	Yes	Yes	Yes
Hyperinsulinemia	Yes	Yes	Yes	Yes	Yes
Childhood obesity	Yes	Yes	Yes	Yes	Yes
Short stature	Yes	Yes	Yes	Yes	Yes
Hyperlipidemia	Yes	Yes	Yes	Yes	No
Normal intelligence	Yes	Yes	Yes	Yes	Yes
Normal extremities	Yes	Yes	Yes	Yes	Yes
Normal karyotype	Yes	Yes	Yes	Yes	Yes
Type 2 diabetes mellitus	Yes	No	Yes	No	No
Subcapsular cataract	Yes	Yes	No	Yes	Yes
Hypogonadism/mestrual irregularities	Yes	No	Yes	Yes	Yes
Cardiomyopathy	No	Yes	No	No	No
Hypotiroidism	No	Yes	No	No	No
Growth hormone deficiency	Yes	Yes	No	No	Yes
Liver dysfunction	Yes	No	No	No	No
Kidney failure/microalbuminuria	Yes	Yes	Yes	No	No
Acanthosis nigricans	Yes	Yes	Yes	Yes	No
Pneumopathy/lung involvement	No	Yes	No	No	No
Alopecia / Flat feet	No/yes	No/no	Yes/yes	Yes/yes	Yes/yes
Kyphosis-Scoliosis / Muscle dystonia	Yes/yes	Yes/no	Yes/no	Yes/no	Yes/no
Advanced bone age	No	Yes	No	No	No

P1: female, 33 years. P2(†): female, 13 years. P3: male, 23 years. P4: male, 33 years. P5: male, 22 years.