Alstrom syndrome other diagnostic studies

Jump to: navigation, search

Alstrom syndrome Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Differentiating Alstrom syndrome from other Diseases

Epidemiology and Demographics

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Tertiary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Alstrom syndrome other diagnostic studies On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

slides

Images

American Roentgen Ray Society Images of Alstrom syndrome other diagnostic studies

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Alstrom syndrome other diagnostic studies

CDC on Alstrom syndrome other diagnostic studies

Alstrom syndrome other diagnostic studies in the news

Blogs on Alstrom syndrome other diagnostic studies

Directions to Hospitals Treating Alstrom syndrome

Risk calculators and risk factors for Alstrom syndrome other diagnostic studies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]; Raviteja Guddeti, M.B.B.S. [3]

Overview

The diagnosis of Alström syndrome relies primarily on clinical findings and/or family history. In some instances the diagnosis can be confirmed by molecular genetic testing. Sequence analysis of the coding region should be performed: tiered testing with sequencing of select exons first, followed by analysis of the entire gene. The frequency of deletions is unknown but deletion/duplication analysis may be clinically indicated in some instances[1].

Other Diagnostic Studies

Molecular Genetic Testing[2]

Gene Testing Method Detected Mutations
ALMS1[3] Targeted mutation analysis 19-bp insertion exon 16
ALMS1 Sequence analysis of select exons: 16, 10, and 8 Sequence variants
ALMS1 Sequence analysis of entire coding region Sequence variants
ALMS1 Deletion / duplication analysis Exonic and whole-gene deletions

Sensitivity and specificity of the above test are 96% and 100% respectively. Positive and negative predictive values reach 100% for this test. Given the current detection rate, failure to identify a disease-causing sequence variant does not preclude the diagnosis of Alström syndrome[4]. Family members who are possible carriers can be screened for the causative ALMS1 mutations if both mutated alleles have been identified in the index case.

Prenatal Testing

Prenatal diagnosis for at risk pregnancies is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15 to 18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed.

For families in which both the disease-causing mutations have been identified preimplantation genetic diagnosis (PGD) may be available.

Renal Biopsy

Renal biopsy often shows interstitial fibrosis, glomerular hyalinosis, and tubular atrophy.

Liver Biopsy

Liver biopsy reveals varying degrees of steatohepatitis, hepatic fibrosis, cirrhosis, chronic nonspecific active hepatitis with lymphocytic infiltration, patchy necrosis, and fatty liver.

References

  1. Minton JA, Owen KR, Ricketts CJ; et al. (2006). "Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome". J. Clin. Endocrinol. Metab. 91 (8): 3110–6. PMID 16720663. doi:10.1210/jc.2005-2633. 
  2. Hearn T, Renforth GL, Spalluto C; et al. (2002). "Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome". Nat. Genet. 31 (1): 79–83. PMID 11941370. doi:10.1038/ng874. 
  3. Collin GB, Marshall JD, Ikeda A; et al. (2002). "Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome". Nat. Genet. 31 (1): 74–8. PMID 11941369. doi:10.1038/ng867. 
  4. Marshall JD, Hinman EG, Collin GB; et al. (2007). "Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome". Hum. Mutat. 28 (11): 1114–23. PMID 17594715. doi:10.1002/humu.20577. 


Cardiology


Linked-in.jpg