Discussion: Galactosemia a Spectrum of Outcomes

In exploring the questions facing galactosemia, these post are for education and discussion only. It is not medical advice. Every patient is different. Always talk to your medical team about personal medical decisions.

Most people think galactosemia is just a “diet problem.” A pediatric illness..
But our community knows it’s much bigger — and far deeper — than that.

The real issue just dairy.
Diet has been the only treatment and the only focus for decades.

I was personally told for my daughter, “Stay on diet, everything will work out.”
That has not been the truth for our families.

The real issue is what happens inside the cells when the body can’t break down galactose properly.

When galactose gets stuck, it turns into toxic metabolites that stress the brain, liver, ovaries, nerves, and other organs. And this stress begins earlier than most people realize — sometimes before a baby is even born.

This is the simple, honest version of what’s really happening.

1. The Two Toxins Driving the Disease

Everyone makes a different amount of galactose internally.

The average amount an adult produces — independent of diet — is 1–2 grams/day.
This is an average, not a fixed number.

In reality, endogenous galactose production varies person to person.
Illness, growth, puberty, liver metabolism, stress, and genetics may cause some individuals to produce higher-than-average internal galactose, which may help explain the wide variation seen across the galactosemia community.

A: Galactitol — the “balloon filler”

Galactitol pulls water into cells.
A little is okay, but too much makes the cell swell like a balloon in a small box.
This can injure tissues especially sensitive to pressure:

• the lens of the eye

• the brain

• the ovaries

Some people likely exceed their tissue-specific “pressure threshold” — like filling a balloon too much until it bursts.
Not everyone crosses that threshold, and the exact threshold has not yet been scientifically established.

B: Galactose-1-phosphate (Gal-1-P) — the “traffic jam”

Gal-1-P builds up because the GALT enzyme cannot process it normally.

Think of Gal-1-P like a massive traffic jam blocking the main road into the city’s power plant:

• supplies can’t get in

• energy can’t be made efficiently

• everything slows down

Research in cell and animal models shows that high Gal-1-P can:

• disrupt normal energy pathways

• lower phosphate needed for ATP generation

• impair mitochondrial function

Gal-1-P does not stop energy production completely — but it reduces energy efficiency and makes the cell work harder for less fuel.

For a child, this can feel like:

• fatigue

• brain fog

• “hitting a wall”

• slow recovery from stress or illness

This isn’t imagined.
It’s cellular energy strain.

2. Why Some Babies Are Sick at Birth

Most families are never told this:

Babies make galactose inside their own bodies — even before birth.

So even without milk:

galactose → Gal-1-P → galactitol can rise
and some tissues may reach their stress threshold.

This explains why some newborns show:

• tremors

• jaundice

• poor feeding

• cataracts

• metabolic crisis

before any formula or breastmilk.

Threshold theory matters here:
every organ can only take so much stress before it becomes overwhelmed.

3. Why Galactosemia Is a Spectrum, Not “Mild vs Severe”

Every organ has its own breaking point — its own threshold.
Every child reaches those thresholds at different times.

That’s why one child may have:

• speech apraxia

• another has tremor

• another has ovarian insufficiency

• another has mostly fatigue

• another has learning challenges

• another appears stable for years

It’s not random.
It’s which organ crosses its threshold, and when.

Galactosemia isn’t “mild or severe.”
It’s a spectrum disorder because the biology plays out differently in each tissue, each organ, in each patient, at each stage of life.

4. Why Two Kids With the Same Mutation Can Be Completely Different

Even with identical GALT mutations, children can have very different outcomes because of:

• differences in metabolic pathways

• differences in mitochondrial resilience

• differences in antioxidant defenses

• differences in placental support in utero

• differences in how quickly their cells accumulate toxins

• possible modifier genes (not yet identified or studied in galactosemia) some genes protect metobolic outcomes, and other gene increase metabolic stress

This is similar to BRCA in breast cancer:
the main gene matters, but other genes and pathways shape the actual outcome.

The absence of studies does not mean modifiers don’t exist — it only means research has not yet explored them.

5. The Missing Piece No One Talks About: Miscarriages

Miscarriages are almost never tested for metabolic causes.

Based on what we know about toxic metabolite buildup, it is scientifically reasonable to consider that:

Some pregnancies may end because the fetus’s cells reached their metabolic threshold too early.

This doesn’t mean all miscarriages are caused by galactosemia — that would overreach the data.

But we can safely say:

“It is possible that severe, unrecognized forms of galactosemia could contribute to early pregnancy loss, and this area has never been studied.”

Families deserve honesty about this uncertainty.

The Placenta Has a Threshold, Too

The placenta is not just a “pass-through organ.”
It is a high-energy, metabolically active organ that:

• filters nutrients

• regulates sugar levels

• handles oxidative stress

• manages fetal waste

• controls fluid balance

• fuels rapid fetal growth

Because it works so hard, the placenta itself can reach a stress threshold, where:

• metabolic toxins overwhelm it

• oxidative stress damages it

• energy production becomes insufficient

• cellular function becomes impaired

• nutrient and oxygen exchange decreases

Placental thresholds are well-documented in other metabolic disorders:

• diabetes

• PKU

• mitochondrial disorders

• fatty acid oxidation disorders

This may represent the most severe end of the galactosemia spectrum — the pregnancies that never make it to newborn screening.

6. The Simple Truth

Galactosemia is caused by toxic metabolites that build up inside the body and stress organs in different ways, at different times, throughout a person’s life.

Some babies hit their thresholds in the womb.
Some at birth.
Some in early childhood.
Some at puberty.
Some slowly over decades.

This is why our community sees such a wide range of symptoms and stories — and why diet alone cannot prevent long-term complications for some children.

The body continues producing galactose internally every day of life.

Our families have lived this truth for years.
Science is finally beginning to catch up.

Plain-Language One-Sentence Summary

Galactosemia is a disorder of toxic metabolite buildup, where galactitol and Gal-1-P place different levels of stress on different organs, creating a wide spectrum of outcomes based on when and where each patient’s cells reach their threshold.

References

• Hasković, M., et al. Pathophysiology and targets for treatment in hereditary galactosemia. JIMD (2020).

• Succoio, M., et al. Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment. (2022).

• Machado, C. M., et al. Galactose-induced phosphate depletion and energy stress in yeast models. (2017).

• Machado, C. M., et al. Galactose-1-phosphate inhibits cytochrome c oxidase and causes mitochondrial dysfunction. (2024).

• Dhaunsi, G. S., et al. Gal-1-P modulates mitochondrial function in neonatal fibroblasts. (2025).

• Jumbo-Lucioni, P., et al. Oxidative stress contributes to outcome severity in Drosophila galactosemia model. (2013).