GALACTOSEMIA-I
DEFINITION:
A disorder of galactose metabolism characterized by a deficiency
of galactose-1-phosphate uridyl transferase activity resulting in
toxic injury to the brain, liver, kidneys, and ovaries.
EPIDEMIOLOGY:
- incidence: 1/50,000
- age of onset:
- whenever galactose-containing foods are introduced into the
diet
- risk factors:
- familial - autosomal recessive
- chrom.#: 9p13
- gene: galactose-1-phosphate uridyl transferase
- M = F
PATHOGENESIS:
- galactose-1-P uridyl transferase catalyzes the conversion of
galactose-1-phosphate to glucose-1-phosphate
- lactose disaccharide -> glucose and galactose
2. Genetic Defect
- genetic defect -> deficiency of galactose-1-P uridyl
transferase activity -> accumulation of galactose-1-P -> injury
to the paren-chymal cells of the kidney and liver, brain,
ovaries, and eyes:
- liver -> cirrhosis
- kidneys -> Fanconi Syndrome
- brain -> mental retardation
- ovaries -> primary or secondary amenorrhea
- eyes -> cataracts
- injury may begin prenatally by transplacental galactose
derived from the diet of a heterozygous mother
- some of the excess galactose is converted into galactitol
and it is this latter compound which can cause cataracts
- accumulation of galactose and galactose-1-P may be toxic to
the ovaries (but not the testes) -> hypergonadotropic
hypogonadism -> primary or secondary amenorrhea
CLINICAL FEATURES:
- lethargy, irritability, vomiting, seizures
- feeding difficulties, poor weight gain, failure to thrive (FTT)
- jaundice, hepatomegaly, hypoglycemia
- ascites, splenomegaly
- hepatic cirrhosis +/- complications
2. Fanconi Syndrome
- episodes of vomiting, dehydration, weakness, & unexplained
fever
- anorexia, constipation
- polydipsia and polyuria
- FTT and growth failure
- rickets
3. Other Manifestations
- mental retardation
- seizures
- speech problems
- pseudotumor cerebri
2. Endocrine
- ovarian dysfunction with primary or secondary amenorrhea
- ? increased risk of ovarian cancer
3. Ocular
4. Infectious
- high frequency of neonatal death due to fulminant E. coli
sepsis (galactose inhibits the bacteriocidal activity of
leukocytes)
INVESTIGATIONS:
- test for reducing substances after feeding human or cow's
milk or formula containing lactose
- positive for reducing substance (galactosuria)
- positive Clinitest but negative Clinistix indicates that
the reducing substance is not glucose
- galactose identified by chromatography
2. Serum
- conjugated hyperbilirubinemia
- elevated transaminase
- elevated FSH and LH with decreased estrogen
- normal lipids and uric acid
- anemia (in the newborn period)
3. Liver Biopsy
- fatty infiltration
- pseudoacini
- macronodular cirrhosis
4. Galactose Tolerance Test
- contraindicated as a sudden galactose load will result in a
high intracellular concentration of galactose-1-P which competes
with glucose-1-P for phosphoglucomutase -> impairs the
conversion of glycogen to glucose -> sudden hypoglycemia +/-
shock, seizures, coma, death
5. Diagnosis
- deficiency of galactose-1-P uridyl transferase activity in
RBC's (on a spot blood test)
- increased concentration of galactose-1-P in RBC's
6. Fanconi Syndrome
- normal anion gap hyperchloremic metabolic acidosis (with
low serum bicarbonate)
- normal or low amino acids
- normal glucose
- hypophosphatemia, hypokalemia, hypouricemia
- elevated alkaline phosphatase
2. Urine
- generalized (non-specific) hyperaminoaciduria
- glycosuria, phosphaturia
- pH < 5.5 with low specific gravity (hyposthenuria)
- bicarbonaturia, hyperkaliuria, uricosuria, tubular
protein-uria, carnitinuria, low urinary ammonia
3. Imaging Studies
MANAGEMENT:
- eliminate lactose and galactose from the diet
- control seizure activity
- multidisciplinary approach:
- Paediatrics, Neurology, Ophthalmology, Endocrinology,
- Genetics, Speech Therapy
2. Fanconi Syndrome
- manage underlying disorder
3. Prognosis
- even with good dietary control there may be poor
intellectual function (females > males), speech problems, and
ovarian dysfunction
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