chemistry

Fumarase deficiency

Fumarase deficiency is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Fumarase deficiency rather than just read about it. In short: Fumarase deficiency (or fumaric aciduria) is an exceedingly rare autosomal recessive metabolic disorder in the Krebs cycle, characterized by a deficiency of the enzyme fumarate hydratase, which causes a buildup of fumaric acid in the urine and a deficiency of malate. Only 13 cases were known worldwide in 1990, after which a cluster of 20 cases were documented in the Short Creek Community located in Arizona, US, that…

Key takeaways

Fumarase deficiency belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Fumarase deficiency to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Fumarase deficiency from memory before moving on to harder problems.

Reference excerpt

Fumarase deficiency (or fumaric aciduria) is an exceedingly rare autosomal recessive metabolic disorder in the Krebs cycle, characterized by a deficiency of the enzyme fumarate hydratase, which causes a buildup of fumaric acid in the urine and a deficiency of malate. Only 13 cases were known worldwide in 1990, after which a cluster of 20 cases were documented in the Short Creek Community located in Arizona, US, that has practiced successive endogamy.

Presentation Fumarase deficiency causes encephalopathy, severe intellectual disabilities, unusual facial features, brain malformation, and epileptic seizures due to an abnormally low amount of fumarase in cells. It can initially present with polyhydramnios on prenatal ultrasound. Affected neonates may demonstrate nonspecific signs of poor feeding and hypotonia. Laboratory findings in neonates may indicate polycythemia, leukopenia, or neutropenia. As they age, neurological deficits begin to manifest with seizures, dystonias, and severe developmental delay.

Pathophysiology Fumarase deficiency is caused by a mutation in the fumarate hydratase (FH) gene in humans, which encodes the enzyme that converts fumarate to malate in the mitochondria. Other mutant alleles of the FH gene, located on human chromosome 1 at position 1q42.1, cause multiple cutaneous and uterine leiomyomata, hereditary leiomyomatosis and renal cell cancer. Fumarase deficiency is one of the few known deficiencies of the Krebs cycle or tricarboxylic acid cycle, the main enzymatic pathway of cellular aerobic respiration.

The condition is an autosomal recessive disorder, and it is therefore usually necessary for an affected individual to receive the mutant allele from both parents. A number of children diagnosed with the disorder have been born to parents who were first cousins. It can also be associated with uniparental isodisomy.

Diagnosis

Treatment

Epidemiology Fumarase deficiency is extremely rare – until around 1990 there had only been 13 diagnosed and identified cases worldwide. A cluster of 20 cases has since been documented in the twin towns of Colorado City, Arizona, and Hildale, Utah, both of which were formerly known as "Short Creek" (or the Short Creek Community). The two towns combine to form a community of 10,000 members of the Fundamentalist Church of Jesus Christ of Latter Day Saints (FLDS) who have a history of practicing successive endogamy, or marriage within their own communities. Nicknamed "Polygamist's Down's", the syndrome has been blamed on cousin marriage, but in a larger sense is related to the reproductive isolation of a community among whom 85% are blood relatives of John Y. Barlow and/or Joseph Smith Jessop (the cofounders of the Short Creek Community). Since the initial cluster from FLDS communities was reported, it is now estimated that there are 100 documented cases worldwide.

See also Hereditary leiomyomatosis and renal cell cancer Founder effect

References

Further reading Pithukpakorn, Manop; Toro, Jorge R. (November 2, 2010) [July 31, 2006]. "Hereditary Leiomyomatosis and Renal Cell Cancer". GeneReviews. Seattle WA: University of Washington. PMID 20301430.

External links

Illustrations

Worked examples

Example 1 — a first encounter with Fumarase deficiency

Start with the simplest possible case. Write down what Fumarase deficiency claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Fumarase deficiency before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Fumarase deficiency ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Fumarase deficiency

In research: Fumarase deficiency appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Fumarase deficiency in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Fumarase deficiency is common in secondary-school and first-year university syllabi. It links to neighbouring topics Amino acid metabolism disorders, Autosomal recessive disorders, Disorders causing seizures, so understanding it makes those chapters shorter.
In everyday life: Look for Fumarase deficiency outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Fumarase deficiency in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Fumarase deficiency means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Fumarase deficiency out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Fumarase deficiency in simple terms?

Why does Fumarase deficiency matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Fumarase deficiency?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Fumarase deficiency.