Abstract Details

Session title: Comorbidities

Session type: Poster - Basic and Clinical Science

Track: Basic and Clinical Science

Presentation number: P-0572

Abstract title:
Hypergonadotrophic hypogonadism in 2 siblings with DIDMOAD syndrome and its associations

Presenting Author: Sinha A K

Background

Wolfram syndrome is a rare hereditary or sporadic neurodegenerative disorder also known as DIDMOAD [WFS1 gene mutations - encodes an endoplasmic reticulum membrane protein called 'Wolframin'' that is expressed in pancreatic beta cells and neurons.]. The classically described presentation is of insulin- dependent diabetes [non-autoimmune], followed by optic atrophy, central diabetes insipidus, and sensory neural deafness. Also included are less well-described presentations of Wolframs syndrome [Neurological and psychiatric manifestations; delayed puberty, central hypogonadism and other anterior pituitary hormone dysfunctions - secondary adrenal insufficiency; urodynamic abnormalities, limited joint motility, cardiovascular and gastrointestinal autonomic neuropathy; heart malformations; etc].

Aim

To describe hypergonadotrophic hypogonadism in the rare genetic autosomal recessive syndrome (Wolfram Syndrome) in 2 sisters.

Method

A.	Sibling 1: Full term normal delivery; Age 8 y: Diabetes insulin dependent.

B.	Sibling 2: Full term normal delivery; Age 4 y: Diabetes insulin dependent.

Results

A.	Sibling 1: Full term normal delivery; Age 8 y: Diabetes insulin dependent; Age 12 y: Optic Atrophy; Age 18: Diabetes insipidus; Age 16: Menarche; Age 17: Secondary amenorrhoea, Serum FSH 87.59 mIU/ml, LH 29.96 mIU/ml, Testosterone 6.88 ng/dl, US Abdomen: small sized uterus, bilateral ovaries hypoplastic / agenesis; Age 17: Bilateral minimal high frequency sloping hearing loss [Right ear PTA 25db, Left ear 22.2 db]. Short Stature: Height cm 146; percentile 0.402; Weight kgs: 29.4, percentile 0.10; Serum Growth Hormone post clonidine: 6.99 ng/ml.

B.	Sibling 2: Full term normal delivery; Age 4 y: Diabetes insulin dependent; Age 15 y: Optic Atrophy; Age 17: Diabetes insipidus; Age 15: Menarche; Age 16: Secondary amenorrhoea, Serum FSH 87.8mIU/ml, LH 21.78mIU/ml, Testosterone 16.25ng/dl, US Abdomen: small sized uterus, bilateral ovaries hypoplastic / agenesis, left side hydronephrosis; Age 16: Left minimal hearing loss, Right normal hearing [Right ear PTA 10db, Left ear 16db]. Short Stature: Height cm 151;percentile 2.928; Weight kgs: 40.2,percentile 0.14; Serum Growth Hormone post clonidine: 7.94 mg/ml.

Discussion

Wolframs syndrome being a progressively devastating multisystem degenerative disorder can have myriad other manifestations than the classically described features; premature death occurs by the fourth decade of life. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotrophic [more reports in males]. Genetic and biologic basis for the diversity in clinical manifestations [including hypogonadism] in Wolframs syndrome needs better elucidation.