2009 Vienna - European Society of Human Genetics

Metabolic disorders
catepe University, Department of Medical Genetics, Turkey, 3 Department of
Internal Medicine, Turkey, 4 Department of Physical Medicine and Rehabilitation,
Turkey, 5 Department of Internal Medicine, Turkey, 6 Department of Biochemistry,
Turkey, 7 Department of Microbiology, Turkey, 8 Department of Physical Medicine,
Turkey, 9 Department of Medical Genetics, Turkey.
FMF is hereditary illness. Although it was reported in one study that
bone mineral density was decreased in child patients with FMF, but the
effect of FMF on BMD is not known in adult patients. The aim of this
study is evaluation of the effect of FMF on BMD in adult patients.
Based on the Livneh criteria 23 FMF patients and control group with
15 people admitted to the study. Exclusion criteria were taking steroid
for a long time, chronic renal failure, woman in post menopause. The
body mass index, BMD (between L1-L4), and Z scores were measured
in both groups. In addition to this taking drug period and illness duration
were taken into consideration in FMF patients. BMD and the other
parameters were compared between groups. After that BMD related
parameters were evaluated.
The mean age of FMF patients (10-female, 13-male) and control group
(10-female, 5-male) was 30.5±8.2(18-48) years and 35.0±10.2(22-54)
years respectively. All of the women in both groups were premenopausal.
There was no difference between two groups for the mean
age, gender and BMI. But FMF patients have had statistically significant
reduction in BMD (between L1-L4) and Z-scores (p=0.015 and
p=0.010 respectively). No statistically significant correlation was found
between BMY and age, BMI, illness duration in the FMF population.
FMF that have episodic inflammation bring about to decrease in BMD.
In our study we didn’t find any factor effective on BMD. Factors that
could be affecting the BMD should be research in the big population.
P13.16
Variants in the FtO gene associate to hyperandrogenemia and
metabolic parameters in polycystic ovary syndrome
E. Wehr 1 , N. Schweighofer 1 , M. Graupp 1 , A. Giuliani 2 , D. Kopera 3 , T. R. Pieber 1 ,
B. Obermayer-Pietsch 1 ;
1 Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine,
Medical University Graz, Austria, 2 Department of Obstetrics and Gynecology,
Medical University Graz, Austria, 3 Department of Dermatology, Medical
University Graz, Austria.
Background: Variants in the fat-mass and obesity associated gene
(FTO) are associated with obesity and type 2 diabetes. Women with
polycystic ovary syndrome (PCOS) frequently present with obesity and
impaired glucose tolerance. The aim of this study was to investigate
the impact of FTO variants on metabolic and endocrine parameters in
PCOS women.
Methods: We genotyped single nucleotide polymorphism rs9939609
(T/A) in 179 PCOS women and 126 female controls. We performed
metabolic and hormonal measurements, oral glucose tolerance test,
hirsutism score, and lipometry.
Results: The A allele was associated with significantly increased
free testosterone (p=0,026), FAI (p=0,042), weight (p=0,006), BMI
(p=0,008), waist (p=0,035) and hip circumference (p=0,041), and triglycerides
(p=0,032). In logistic regression, the A allele was associated
with free testosterone (p=0,032; OR 1,7; 95% CI 1,05-2,9; B=0,76).
Total fat mass (p=0,007), visceral adipose tissue mass (p=0,013), subcutaneous
fat mass (p=0,007), and lean body mass (p=0,007) were
significantly increased in PCOS women carrying the A allele. The A/
T+A/A genotype showed increased prevalence in overweight/obese
PCOS patients (OR=2,5; p=0,006) and in PCOS women with impaired
glucose tolerance (OR=3,6; p=0,017). No significant association was
seen between FTO variants and the PCOS per se.
Conclusion: In summary, we demonstrated that FTO variants influence
hyperandrogenemia and anthropometric parameters in women with
PCOS, indicating an important role of FTO variants not only in obesity
and diabetes but also in hyperandrogenism in women with PCOS.
P13.17
Biochemical and molecular diagnosis of Galactosemia in iranian
patients
M. Bahar1 , M. Houshmand2 , H. Aryan1 ;
1 2 Iranian Burn Center, Tehran, Islamic Republic of Iran, special medical center,
Tehran, Islamic Republic of Iran.
Classical galactosemia is an inborn metabolic disorder caused by autosomal
recessive mutations in galactose 1 phosphate uridyl transfer-
ase (GALT) gene. The incidence of the disease varies from 1:40000-
1:60000 among Caucasian population. To date, over 170 different mutations
have been reported including point mutations, microdeletions
and insertions. The most frequent reported mutation is Q188R which
accounts for approximately 60% of mutant alleles in Caucasian population.
In the present investigation, results of a 5-year study on galactosemia
in Iran including biochemical diagnosis and molecular analysis of
GALT gene are presented.
Methods: Twenty five galactosemia patients were subjected to diagnosis
of galactosemia by the determination of GALT activity in RBCs using
Beutler test. DNA samples were investigated for the 5 most reported
mutations including Q188R, K285N, X380R, L195P and Q169K using
PCR-RFLP method. PCR-SSCP
method was used for the whole GALT gene including 11 exons and
flanking intronic sequences to investigate the mutations which were
not detected by PCR-RFLP method. In a retrospective study, galactosemic
patients were traced and
their long term outcomes were evaluated.
Results: Q188R mutation was the most observed mutation with the
allelic frequency of 57.1%. The allelic frequencies for S135L, Y209S,
A320T, and K285N were found to be 7.1%, 7.1%,7.1%, and 3.57%,
respectively.
Conclusion: Our results show that galactosemia is a heterogeneous
disorder at the molecular level in Iranian population. Study on long
term outcome of the disease emphasizes the need for a new look and
new challenges for galactosemia in Iran.
P13.18
Gamma-Hydroxybutyric aciduria - identification of first Bulgarian
case by a metabolomic approach
M. B. Ivanova, I. M. Bradinova, R. Vazharova, I. Kremensky;
National Genetic Laboratory, University Hospital of Obstetrics and Gynecology,
Sofia, Bulgaria.
Succinic semialdehyde dehydrogenase (SSADH) deficiency (MIM
271980) is a rare autosomal recessive disorder due to defect in gamma-aminobutyric
acid catabolism, resulting in the accumulation of
gamma-hydroxybutyric acid (GHB) and causing neurological disorders
of varying severity. SSADH is characterized by psychomotor retardation,
childhood-onset hypotonia, and ataxia. Seizures occur in more
than 50% of affected individuals. The diagnosis of SSADH deficiency
is suspected in individuals with gamma-hydroxybutyric aciduria present
on urine organic acid analysis and can be confirmed by assay of
SSADH enzyme activity in leukocytes. ALDH5A1 is the only gene currently
known to be associated with SSADH deficiency.
We report an 11 years old boy, fifth child of a consanguineous roma
family. The patient presented with severe psychomotor retardation after
birth. Later on he developed seizures. His older sister, the fourth
child of the family has similar clinical signs of profound mental retardation
and seizures. The boy died with severe dehydratation and epileptic
status during an ongoing infection.
Preinvestigation findings were abnormal urine ketones; metabolic profile
by GC/MS organic acid analyses in urine showed marked excretion
of GHB and 3,4-dihydroxybutiric acid. Ketonuria and dicarboxiclic
aciduria were detected. SSADH enzyme activity have not been investigated
because leukocytes are not available.
Substantial excretion of GHB against the background of the family history
and the clinical phenotype suggest succinic semialdehyde dehydrogenase
deficiency. The significant amounts of dicarboxylic acids
in the urine may indicate a secondary inhibition of mitochondrial fatty
acid beta-oxidation or propionyl-coenzyme A metabolism by succinic
semialdehyde or its metabolites.
P13.19
Gaucher‘s disease type I - cytokines profile
M. D. Grigorescu, P. Grigorescu-Sido, A. Cristea, V. I. Pop;
UMF Iuliu Hatieganu Cluj-Napoca, Cluj-Napoca, Romania.
Aim: The paper proposed to investigate the dynamics of the serum
levels of cytokines in a group of patients with Gaucher disease in correlation
with the severity score index and skeletal involvement. Patients
and methods: The group included 15 patients with Gaucher
disease aged between 10-53 years; the diagnosis was based on clini-