inborn vs inherited

[ValWood]

inborn errors of metabolism MONDO:0019052

Definition	Parents

A group of disorders present at birth that involve genetic defects leading to disturbances in carbohydrate, lipid, lysosomal storage or amino acid metabolism in the body. The inborn errors of metabolism are typically rare, but this class also encompasses non-rare diseases like hereditary hemochromatosis type 1

What does "present at birth" mean ? how does it differ from 'inherited"? does this mean that the disease is already visible, or something else?

for example, hemochromatosis type 1 in the def does not manifest until middle age?

[nicolevasilevsky]

I think 'present at birth' is different from inherited in that it doesn't necessarily have to be an inherited disease, but could be a disease that arose via a different mechanism.

There is a comment on MONDO_0006507 'hereditary hemochromatosis' (which is the parent of hemochromatosis type 1): Editor notes: HH1 is not rare, so the current placement of generic HH under rare inborn errors of metabolism is technically incorrect. However, reclassifying on the basis of prevalence does not make biological sense since the mechanism is the same. See notes on MONDO:0019052

The def of MONDO_0019052 'inborn errors of metabolism' is: A group of disorders present at birth that involve genetic defects leading to disturbances in carbohydrate, lipid, lysosomal storage or amino acid metabolism in the body. The inborn errors of metabolism are typically rare, but this class also encompasses non-rare diseases like hereditary hemochromatosis type 1

More towards your question - I don't see mention of middle age onset in the def of MONDO_0021001 hemochromatosis type 1 def: Hemochromatosis type 1 (classic) is the most common form of hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition. Due to its incidence (1/200-1/1000), it is not considered as a rare disease, unlike the other subforms of the disease

[nicolevasilevsky]

@pnrobinson or @cmungall do you want to weigh in?

[ValWood]

I think 'present at birth' is different from inherited in that it doesn't necessarily have to be an inherited disease, but could be a disease that arose via a different mechanism.

So what would an example of another mechanism be other than "inherited"?

Hemochromatosis type 1 is inherited, autosomal, recessive but not "present at birth"

[pnrobinson]

Exactly. For instance congenital infection (https://med.emory.edu/departments/pediatrics/divisions/neonatology/dpc/conginf.html).

inborn and inherited are synonymous (for all effective purposes). Not all inborn defects manifests at birth congenital means something that manifests at birth

[ValWood]

congenital means something that manifests at birth

So can you use "congenital" for everything that is currently "manifests at birth" (Or did I misunderstand which part this was the answer too.

More towards your question - I don't see mention of middle age onset in the def of MONDO_0021001 hemochromatosis type 1

hemochromatosis type 1 is definitely not ever symptomatic at birth

"Haemochromatosis is an inherited condition where iron levels in the body slowly build up over many years. This build-up of iron, known as iron overload, can cause unpleasant symptoms. If it is not treated, this can damage parts of the body such as the liver, joints, pancreas and heart." "only a small proportion of people with 2 copies of the faulty HFE gene will ever develop the condition" https://www.nhs.uk/conditions/haemochromatosis/

I'm still a bit confused if "present at birth" refers to the mutation or the symptoms but I'm new to this. It could be clearer.....

i.e if it means only inherited why not say 'inherited' and if it means "visible from birth" say congenital. Or isn't it that simple?

[pnrobinson]

an inherited condition does NOT mean visible at birth. Essentially it means in this context that the affected person carries genetic variants that strongly (and in many cases deterministically) predispose to health problems later in life.

[ValWood]

an inherited condition does NOT mean visible at birth.

No, clearly. But I said "i.e if it means only inherited why not say 'inherited'"

if "present from birth" means more than inherited, what is that? This is the part that I am not getting.

[pnrobinson]

I see what you mean. AFAIK this is a question of usage. The Inborn errors or metabolism refer to a group of very serious disorders that happen to also present at birth. They result from defects in enzymes that are basically required from birth on. This is an additional specification.

[ValWood]

OK, so action is to review those which are described as "inborn"

inborn disorder of purine or pyrimidine metabolism (MONDO:0019254)

includes things which are not severe at birth

Definition	Parents

A group of disorders present at birth that involve genetic defects leading to disturbances in carbohydrate, lipid, lysosomal storage or amino acid metabolism in the body. The inborn errors of metabolism are typically rare, but this class also encompasses non-rare diseases like hereditary hemochromatosis type 1

and the definition includes hemochromatosis type 1 as a specific example which is definitely not inborn based on this additional criteria. Hemochromotosis never has observed symptoms at birth because by definition it is an iron overload disorder.

[pnrobinson]

Might be easier to skype. inborn means hereditary not congenital, and thus inborn is correct here!

[ValWood]

Yes, I can't do today as I'm supposed to be off, it's bank holiday here. I just got caught up in some "small tasks'

So far summarizing I'm getting

hereditary --congenital --inborn (hereditary but not congenital) --other?

but then

• inborn and inherited are synonymous (for all effective purposes).
• Not all inborn defects manifests at birth
• The Inborn errors of metabolism refer to a group of very serious disorders that happen to also present at birth. They result from defects in enzymes that are basically required from birth on.

It just that these statements seems to be conflicting.

• Congenital disorders are present from birth.
• Inborn disorders are non-congenital disorders.
• Some inborn disorders are present from birth (so some inborn disorders are congenital?)

[ValWood]

I think I get it now.

So inborn errors of metabolism (MONDO:0019052) could have exact synonym "inherited metabolic disease"

is that correct? I was just wondering why sometimes inherited is used, and sometimes inborn is used?

[ValWood]

No I am still getting it wrong

Definition	Parents

Diseases caused by abnormal function of the mitochondria. They may be caused by mutations, acquired or inherited, in mitochondrial dna or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.

so inherited is narrower than inborn?

Maybe it doesn't matter for the ontology. I just wanted to know because I can't check our groupings sensibly unless I understand what the term names/definitions mean.

Happy for a Skype explanation sometime.

[pnrobinson]

@ValWood if you would like to send me an email, I'd be happy to set up a skype.

I think that inborn and inherited are very close, but inborn tends to be used to describe a disease that is caused by an inherited mutation. The word is not much used any more, I think we mainly see it in inborn errors of metabolism.

Another point is that we should avoid the use of the word mutation (the community is rejecting this word and prefers variant with a modifier...)

[ValWood]

I just spoke with @pnrobinson and I was going to say this ticket could close.

But I see the problem I first reported.

According to Peter, inborn is synonymous with inherited, but this definition says "present at birth"

inborn errors of metabolism MONDO:0019052 Definition A group of disorders present at birth that involve genetic defects leading to disturbances in carbohydrate, lipid, lysosomal storage or amino acid metabolism in the body. The inborn errors of metabolism are typically rare, but this class also encompasses non-rare diseases like hereditary hemochromatosis type 1

BUT the inborn errors of metabolism MONDO:0019052 are NOT necessarily present from birth.

So the definition SHOULD change,

Could it say instead A group of ~disorders present at birth~ inherited disorders?

that would fix the problem!

[nicolevasilevsky]

Yes, I'll fix this. thanks @ValWood! Glad you and Peter were able to catch up.

[ValWood]

I would like @pnrobinson to confirm first, but this is my understanding.

Sorry that I missed chatting to you too!

[pnrobinson]

I would suggest this definition: Inborn errors of metabolism are rare inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or organelle function.

The following is not true: The inborn errors of metabolism are typically rare, but this class also encompasses non-rare diseases like hereditary hemochromatosis type 1

[ValWood]

I agree, I'm HFE-/HFE-, iron overload isn't a metabolic disorder ;)

[nicolevasilevsky]

sounds good, I updated the def to: Rare inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or organelle function.

Chris asked that we not replicate the name of the class in the definition in his blog

[cmungall]

Technically the def is still not right as it says "rare" yet HH1 is not rare... but this is a "rare" exception (where "rare" applies at the metaclass level...)

[nicolevasilevsky]

Shall we revise to 'Inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or organelle function.' ?

[pnrobinson]

Nicole's suggestion seems fine. Possibly we should de-pluralize the definition thought. An inherited disorder resulting... since we are striving to be singular!

[nicolevasilevsky]

Thanks, I will fix this!

[ValWood]

inborn errors of metabolism MONDO:0019052 Would it also be clearer, because of the confusion, to standardize term names on "inherited" and have "inborn" as exact synonym?

[pnrobinson]

For whatever reason, the word inborn seems to be used solely in this context and it would probably engender even more confusion if we use it in other contexts.

[ValWood]

I'm still a bit confused.

2. The term inborn errors of metabolism

is now defined Inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or organelle function.

and has inherited disorders of metabolism as an exact synonym? Is that correct?

3. If this is the case it still seems that using "inherited errors of metabolism" would be a more universally understandable term name? or do people more commonly use "inborn" especially since here: https://github.com/monarch-initiative/mondo/issues/1483#issuecomment-628568249 @pnrobinson you say that 'inborn' is not used very much anymore (Note that I am not suggesting using 'inborn' in other contexts. I am suggesting the opposite, that you 'demote' the use of 'inborn' because it is confusing, if it means the same).

Google "inborn metabolic disorder" About 14,200 "inborn disorders of metabolism" 2,620 "inherited disorders of metabolism" About 65,100 "inherited metabolic disorder" About 113,000 results

[pnrobinson]

I am saying just for this group of diseases use the word inborn, and have inherited as a synonym. The other synoynms are also fine.

[nicolevasilevsky]

I updated the definition and added the synonyms inherited disorder of metabolism, inborn disorders of metabolism, inborn metabolic disorder, inherited disorders of metabolism