Classic Galactosemia

Biochem lec prefinals

What enzyme is deficient in classic galactosemia

Galactose 1 phosphate uridyltransferase (GALT)

What is the consequence of GALT deficiency

Block in conversion of galactose → glucose; accumulation of toxic galactose 1 phosphate and metabolites

When do symptoms usually appear

In newborns after ingestion of lactose-containing milk

Inheritance pattern of glactosemia

Autosomal recessive

How common is classic galactosemia

1 in 30-60 thousand births

Which population has the highest prevalence

Europeans (less common in asians)

Do males or females get affected more often?

Both equally (autosomal inheritance)

What happens without early detection/ treatment

High neonatal mortality due to liver failure and sepsis

What accumulates and becomes toxic to tissues in GALT deficiency

Galactose 1 phosphate

Why does excess galactose cause cataracts

Converted into galactitol, which deposits in the lens

How does metabolite accumulation affect the liver

Causes hepatic failure, jaundice, hepatomegaly, and bleeding tendencies

What long-term effects does galactose 1 phosphate buildup have

Interferes with cell signaling and glycosylation → neurocognitive deficits, speech problems, ovarian failure

When do symptoms typically present

Within the first few days of life after milk ingestion

What are the early signs

Poor feeding, vomiting, diarrhea, lethargy, irritability, failure to thrive

Major systemic manifestations

Liver: jaundice, hepatomegaly, failure, bleeding

Kidney: aminoaciduria, acidosis

Eye: cataracts

Infection: high risk of neonatal E. coli sepsis

Long term complications despite treatment

Speech/ language delay, developmental delay, tremors/ poor coordination, premature ovarian insufficiency (females), Osteopenia/ osteoporosis

how is galactosemia usually detected?

Newborn screening (low/absent GALT activity or high galactose/ galactose 1 phosphate)

What is the gold standard diagnostic test

Enzyme assay measuring GALT activity in RBCs

What urine test may be positive

Benedict’s test (detects reducing substances, but nonspecific)

How can diagnosis be confirmed

Genetic testing of the GALT gene

What is the immediate step when galactosemia is suspected?

Stop breastfeeding/ standard formula; switch to soy-based or lactose free formula

What is the long-term treatment

lifelong galactose/ lactose-restricted diet; avoid dairy and hidden galactose

Why are calcium and vitamin D supplements needed?

to prevent bone disease from dairy restriction

What monitoring is required long-term

Growth, liver function, cataracts, speech/language development, neurocognition, ovarian function (in females)

Who should be involved in ongoing care

Multidisciplinary team (pediatrician, dietitian, speech therapist, endocrinologist, genetic counselor)

Galactosemia

is life treating