What Is Hawkinsinuria?
Hawkinsinuria is an autosomal dominant inherited disorder characterized by the presence of specific amino acids like hawkinsin in the urine. The condition arises due to the inability of the body to break down the amino acid tyrosine. The disease is commonly diagnosed in infants after they discontinue breastfeeding. The condition develops due to gene mutation in the HDP gene.
Hawkinsinuria is also called:
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4-HPPD deficiency.
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4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency.
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4-hydroxyphenylpyruvic acid dioxygenase deficiency.
The above names are based on the deficiency of the amino acids that leads to the condition. The complete absence of these amino acids leads to a similar genetic condition called tyrosinemia which also presents difficulty metabolizing tyrosine but with a different etiology as it is caused due to mutations in the fumarylacetoacetate hydrolase (FAH) gene, which is responsible for the production of the FAH enzyme.
What Are the Symptoms of Hawkinsinuria?
Hawkinsinuria is manifested during early childhood in infants; some of the common symptoms of the disease include:
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Swimming pool or chlorine-like odor of the urine.
The condition affects various systems of the body:
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Hair: Thin and sparse hair.
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Muscle: Abnormal muscle tone or hypotonia; the muscles remain in a constant state of contraction even when in a state of rest.
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Thyroid: Hypothyroidism.
The symptoms appear when the child discontinues having breast milk and is shifted to other formulations.
In the later stages of life, as the child grows up and leads a normal life without any restrictions or complications, the only symptom observed throughout the life is the chlorine or swimming pool odor of the urine as the individual continues to excrete tyrosine throughout the life.
What Are the Causes of Hawkinsinuria?
Hawkininuria is an autosomally inherited disorder that has an autosomal dominant pattern of inheritance of the disease, and the disease is caused due to A33T mutation in 4-hydroxyphenylpyruvic acid dioxygenase (4-HPPD). This enzyme that catalyzes the conversion of hydroxyphenylpyruvate to homogentisate. Autosomal refers to an inheritance pattern where the gene is located on any gene except the sex chromosome; dominant suggests that the disease is expressed even if one of two chromosomes is affected. The inheritance of the disease can be in the following patterns:
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Familial inheritance: Infants with a family history of the condition develop the disease as the mutated gene is passed on from parents to children.
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Mutation of new genes: Children with healthy parents develop the condition due to mutation in the new genes, which can be due to developmental disturbances.
The chances of affected parents passing the disease to their children are about 50 %. The severity of the disease can be the same as parents or be less symptomatic when passed on to the next generation.
How Is Hawkinsinuria Diagnosed?
Hawkinsinuria is a condition that appears when a child stops having mother's milk and is diagnosed accidentally on clinical examination by a detailed history from the parents and characteristic signs and symptoms. The diagnosis is confirmed by urine analysis which detects characteristic tyrosine metabolites in urine on acid analysis.
To prevent complications, newborn screening (NBS) is an essential tool for the early diagnosis and treatment of inborn errors of metabolism and other disorders. Because most hawkinsinuria patients remain asymptomatic during their first weeks of life, altered tyrosine levels are the only finding that can lead to an earlier diagnosis.
The etiology of the disease can be confirmed using molecular studies, which can help in further treatment of the disease.
How Is Hawkinsinuria Treated?
The children affected by the condition have the onset of the symptoms during early childhood when they shift from breastfeeding to the formulations, and the condition results due to the inability of the body to metabolize the amino acid tyrosine, which is a building unit of most of the proteins consumed. Therefore treatment aims at continuing breastfeeding and dietary modifications to minimize the symptoms and discomfort of the patient. Patients with hawkinsinuria are recommended to consume a diet containing a low amount of phenylalanine, tyrosine, and ascorbic acid; these dietary modifications resolve metabolic acidosis, and the person leads a normal life as a grown-up. The presence of disease in older individuals is indicated only by the urine's chlorine-like or swimming pool odor.
Prognosis:
The prognosis of the patients with hawkinsinuria is excellent as the symptoms improve after the first year of life. There are no symptoms or discomfort present during late childhood, even without treatment in cases that are left undiagnosed.
Conclusion:
Hawkinsinuria is a rare acquired genetic disorder that has an autosomal dominant type of inheritance, and the condition is caused due to mutation in the HDP gene; individuals with hawkinsinuria present symptoms during early childhood and are unable to break down amino acid tyrosine which is excreted in urine as hawkinsin and has a characteristic chlorine-like odor. This condition is diagnosed during early childhood during newborn screening or can be unnoticed as the person does not have any symptoms or problems growing up. The condition can be passed on either by the affected parents or can occur due to new mutations. The treatment includes dietary restrictions and is recommended to avoid food containing phenylalanine, tyrosine, and ascorbic acid. However, the prognosis of the disease is good, and thus some people with hawkinsinuria survive even without any treatment.
