Monday, 26 September 2016

Information on DGAT1 Deficiency, its Symptoms and Treatment

Information on DGAT1 Deficiency, its Symptoms and Treatment

The DGAT1 gene encodes an enzyme responsible for re-esterification of the triglycerides in enterocytes. Most medical research has been focused on suppressing the DGAT1 gene for treatment of obesity and related conditions.

Symptoms of DGAT1 Deficiency
Patients with deficiency in DGAT1 show an extreme intolerance to fat of any sort. There are only a handful of known cases globally, but all have shown clear symptoms within days post birth - extreme diarrhoea and vomiting. If left unmanaged, some potential symptoms include:
1. Diarrhea with protein loss
2. Malnutrition with hypophosphatemia
3. Multiple vitamin and mineral deficiencies (copper, zinc, iron, Vitamin D and E)
4. Hyperphosphatemia
5. Elevated transaminases
6. Iron deficiency anaemia
7. Failure to thrive

How do you test for DGAT1
Whole exome sequencing can provide insight into whether an individual has a deficiency of DGAT1. However, in some cases data labs have not picked up on the slight changes to DGAT1 in their reports, and diagnosis have been made post review of the underlying data by GI geneticists.

How do you treat DGAT1
The only known way to manage a DGAT1 deficiency is to almost eliminate all fat from the individual’s diet. Patients have been able to tolerate circa 10g of fat a day, spread across meals. Additional fat has caused explosive diarrhoea, and typically takes 2-3 days for the individual to return to normality.

A case study was done by Boston Children’s Hospital on DGAT1 mutation with reference to identical male twins of South Asian descent with a mutation of DGAT1 gene, 314T>C, p.L105P L105P, with congenital diarrhoea, outline their nutritional management and initial functional analysis.

Clinical Case:
·         Monochorionic male twins born at 36 weeks gestational age by scheduled c-section and developed watery diarrhea and acidosis shortly after birth.
·         Diarrhoea and poor weight gain persisted despite multiple formula changes and gastrostomy tube feeds.
·    Presented at 26-months old with failure to thrive, protein losing enteropathy, hypogammaglobulinemia, vitamin D, and iron deficiencies.
·         Twin A required hospitalization and total parenteral nutrition.
·         An extensive work-up culminated with whole exome sequencing (WES).

·         WES sent from Twin A revealed a homozygous point mutation in the DGAT1 gene, c.314T>C, p.L105P.
·         Confirmation by Gene Dx sequencing and found both parents to be heterozygous for the same mutation.

Dietary Management

Twin A had improved growth and vitamin levels as expected on complete parenteral nutrition. He was transitioned to a low fat diet containing no more than 10% calories from fat. On this diet his protein losing enteropathy was resolved, as evidenced by normal stool alpha-1 antitrypsin and serum immune globulin levels. If his daily fat intake surpasses the 10%, he experiences loose stools. Similarly, his twin brother has improved growth and resolution of protein losing enteropathy on this regimen.


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