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Homocystinuria

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High Yield Notes

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Homocystinuria

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Questions

USMLE® Step 1 style questions USMLE

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An 11-year-old girl is brought to the emergency room after sudden weakness in her right arm and leg and slurred speech. She has complained of intermittent chest pain during gym class and visual disturbances for the past 2 months. Her parent states that the patient’s performance in school has been poor recently. The family immigrated from Singapore 2 years ago. Her birth and development were unremarkable. Weight at the 50th percentile for her age, while height is at the 85th percentile. Temperature is 37.0°C (98.6°F), pulse is 94/min, respirations are 18/min, and blood pressure is 105/65 mmHg. Physical examination reveals kyphosis and pectus excavatum. Ophthalmic examination reveals bilateral lens luxations. Neurological examination reveals 2/5 power in her right upper and lower limb and positive Babinski sign on the right side. An inborn error of metabolism is suspected as the cause of this patient’s symptoms. Which of the following enzymes is most likely deficient in this patient? 

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Atherosclerosis p. 305

homocystinuria as cause p. 83

Homocystinuria p. 83

Marfanoid habitus

homocystinuria p. 83

Myocardial infarction (MI) p. 308

homocystinuria p. 81

Osteoporosis p. 467

homocystinuria p. 83

Stroke p. 525

homocystinuria p. 83

Thrombosis

homocystinuria p. 83

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Content Reviewers

Justin Ling, MD, MS,Yifan Xiao, MD

In homocystinuria, “homocysteine” is a metabolite of the amino acid methionine, and “uria” means, a substance present in urine.

So people with homocystinuria have large amounts of homocysteine in their urine, as well as other problems in the connective tissue, muscles, brain, heart, and blood vessels.

Now, amino acids are the basic building blocks that make up proteins.

There are 20 amino acids used in the human body and they all contain a carboxyl (-COOH) group and an amine (-NH2) group.

Methionine is one of the essential amino acids, meaning our bodies can't create it, but they must be acquired through food that’s rich in protein like meat, eggs, dairy, avocados, beans, etc.

So the proteins you eat are broken down into amino acids in the gastrointestinal tract by gastric acid and digestive enzymes.

The amino acids are then absorbed by the small intestine into the bloodstream, and then travel to the cells of the body, where they are used for protein synthesis.

Since the body can’t store these amino acids, any excess amino acids are converted into glucose or ketones and used for energy.

Now methionine is also used to synthesize another amino acid, cysteine.

First, methionine is converted into the amino acid homocysteine through multiple steps.

Next, the enzyme cystathionine beta- synthase, which requires vitamin B6 as a substrate, combines homocysteine and serine to create cystathionine.

Finally, the enzyme cystathionase converts cystathionine into cysteine.

Any homocysteine that does not undergo this process can be converted back into methionine by methionine synthase, which requires vitamin B12, or cobalamin, and folate as substrates.

There are two types of homocystinuria: familial and acquired.

Familial homocystinuria is an autosomal recessive genetic disorder that first manifests early in life.

It’s usually caused by cystathionine beta-synthase deficiency, but it can also be caused by decreased B12 affinity in cystathionine beta- synthase, or methionine synthase deficiency.

Now, when there’s a problem with cystathionine beta- synthase, homocysteine cannot be combined with serine, so less cysteine is produced, and homocysteine builds up in the body.