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Homocystinuria

What is homocystinuria?

Homocystinuria is a genetic, inherited disorder characterized by high urine and serum homocysteine concentrations (a amino acids) People with homocystinuria cannot adequately process the amino acid metathionine, which is necessary for growth and development in children and to maintain nitrogen balance in adults.

What are the signs and symptoms of homocystinuria?

Newborns with homocystinuria often appear normal, but signs and symptoms begin to develop in the first year of life, although not all are apparent early on.

The signs and symptoms of homocystinuria can vary widely, and patients may have any of the following:

  • Marfanoid appearance (this refers to the tall, slim build and long limbed appearance reminiscent of Marfan syndrome )
  • Pectus carinatum or pectus excavatum (the depression of the protrusion of the sternum)
  • High arched palate with crowding of teeth.
  • Kyphoscoliosis
  • Ectopic lentis (dislocation of the lens)
  • Myopia
  • Glaucoma
  • Mental retardation (with an average IQ of 80, although approximately 30% of patients with homocystinuria have an IQ in the normal range).
  • Arachnodactyly (long and spider fingers)
  • Seizures
  • Cerebrovascular events
  • Psychiatric disorders
  • Osteoporosis
  • Child failure to thrive
  • Increased likelihood of blood clots and deep veins. thrombosis

Cutaneous Signs of homocystinuria include:

  • Hypopigmentation because inhibition of tyrosinase
  • Fair and slim hair
  • Thin, translucent skin
  • Hyperhidrosis

  • Dry skin with a tendency to eczema

  • Vitiligo
  • Flushed cheeks with large pores.
  • Livedo reticularis
  • Atrophic scars on arms and hands
  • Telangiectasia

What Causes Homocystinuria?

Homocystinuria is inherited in a autosomal recessive pattern Mutations from CBS, MTHFR, MTR, MTRR and MMASHC genes have been implicated

These mutations can lead to:

  • cystathionine beta synthase (CBS) deficiency
  • 5,10-methylenetetrahydrofolate reductase deficiency
  • cobalamin deficiency in coenzyme synthesis
  • enzyme abnormalities affecting the conversion of homocysteine to metathionine
Genetics of homocystinuria *

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* Image courtesy of Genetics 4 Medics

How is homocystinuria diagnosed?

Homocystinuria tests may include:

  • Cyanide-nitroprusside test
  • Serum and urine amino acid test
  • Plasma free methionine levels
  • Ophthalmological myopia exam, ectopic lentis

  • Skin biopsy with fibroblasts culture

  • Skeletal x-ray
  • Liver biopsy with enzyme assay.
  • MTHFR genotyping

How is homocystinuria treated?

There is no cure for homocystinuria. However, about half of the patients respond to high doses of pyridoxine (B6). Skin pigmentation You can go back to normal.

For those who do not respond to pyridoxine, other treatments include:

  • A low-metathionine diet (this includes carrots, beets, chard, tomatoes, spinach, bell peppers, melons, apples, pears, but excludes broccoli, mushrooms, avocados, potatoes, walnuts, tofu, and black or black beans, due to the content of amino acids)
  • Trimethylglycine (betaine)
  • Folic acid supplements and addition of cysteine to the diet.

Many patients with homocystinuria die as young adults from arterial and venous thrombosis.