Transferase galactosemia is an autosomal recessively inherited disorder caused by a block in the
conversion of galactose to glucose. Manifestations include jaundice, vomiting, cataracts, mental
retardation, speech abnormalities and poor growth. This disorder is due to a deficiency of galactose-
1-phosphate uridyl transferase (GAIT), an enzyme which catalyses the conversion of
uridyldisphosphoglucose (UDPG) and galactose-l-phosphate to uridyldisphosphogalactose
(UDPGal) and glucose-1-phosphate. The GALT gene has been mapped and 50 mutations have
been reported in this; gene to date.
The aims of this project were to identity and characterise galactosemia-causing mutations in the
South African negroid population and to determine the frequency of these mutations in order to
estimate the incidence of transferase galactosemia in the South African negroid population. Twentysix
negroid patients and one obligate carrier were investigated and the SI35L mutation was found to
account for approximately 91% (48/53) of galactosemia alleles in this group. The estimated S135L
allele carrier frequency in 600 healthy unrelated negroid individuals (1/75) was used in conjunction
with the proportion of non-S135L galactosemia alleles present in galactosemics to arrive at an
estimated galactosemia incidence of 1 per 18 455 births. This is over three times the estimated world
average of one per 70 000.
Three caucasoid galactosemia patients, one galactosemic patient of mixed ancestry and two obligate
carriers (one caucasoid and one of mixed ancestry) were screened for mutations in the GALT gene.
The Q188R mutation was found to account for 57% (4/7) of the galactosemia mutations in the South
African caucasoid galactosemics which is similar to the overall frequency detected in other caucasoid
populations. Both the SDSL and the Q188R mutations were detected in the individuals of mixed
ancestry.
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Several populations from western, central and southern Africa were screened for the SDSL
mutation. This mutation was found at low frequencies (± ISE) in western and central Africa, 0.003
(+2.5 x 10'3) and 0.003 (±1.96 x 10""), respectively and was detected at a higher frequency (+ 1SE) of
0.006 (±2.25 x lO"3) in the southeastern Bantu, but was not detected in the San populations screened.
This mutation also accounts for approximately 48% of the galactosemia mutations in African
American galactosemics. Those results suggest an African origin of the S135L mutation.
The South African negroid galactosemics and 202 randomly ascertained negroid individuals were
screened for the QI88R mutation and &c/RFLP in the GALT gene. The Q188R mutation was not
detected in these groups; thus indicating that this mutation was not a major cause of transferase
galactosemia in South African negroids. No Sad" alleles were detected in these individuals
suggesting that this allele was not associated with the galactosemia mutations in negroids and was
less frequent in this population than in caucasoids. Seventy South African Indians were screened for
the N314D mutation which results in the Duarte electrophoretic phenotype (both Duarte and Los
Angeles alleles result in this phenotype) is associated with the Duarte variants of galactosemia. The
N314D mutation was found at the high frequency (± 1 SE) of 0.20 (± 0.033) in this group and this
mutation was detected in cis with the Sad" allele (Duarte) or in cis with the L218L mutation (Los
Angeles).
A previously undescribed mutation, G to A transition at bp 997 in exon 4 of the GALT gene, was
discovered in a randomly ascertained individual from the Central African Rephiic. This mutation is
predicted to result in the substitution of arginine by glutamine at amino acid IZi, sad did not appear
to affect the level of GALT activity in red blood cells.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/14693 |
| Date | 21 May 2014 |
| Creators | Manga, Nayna |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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