Overview

Barakat syndrome is a rare genetic disease characterized by a triad of symptoms like hypoparathyroidism, sensorineural deafness, and kidney disease. It is also called HDR syndrome.^1,2 The patients show reduced calcium levels in the blood and associated symptoms. Early diagnosis of the disease is crucial for a better prognosis and to improve the quality of life of the patients. This article provides an insight into the clinical symptoms, factors influencing the prognosis, typical progression, and long-term outcome of the disease.

What is Barakat syndrome?

Barakat syndrome is a rare genetic disorder caused by genetic mutations in the GATA3 gene. It is inherited as an autosomal dominant pattern—only one parent needs to have the mutated gene to pass it to the children. The risk of passing the disease to the children is 50%. The rarity of the disease is such that only 200 patients with this disease have been reported worldwide in literature. The GATA3 gene is involved in developing the parathyroid gland, inner ear, kidneys, thymus gland, brain, and spinal cord. Hence, Barakat syndrome presents with classic symptoms like hypoparathyroidism, sensorineural deafness, and kidney disease (HDR) syndrome. The parathyroid hormone helps to regulate calcium levels in the body. Hypoparathyroidism results in reduced calcium levels in the blood and causes associated disorders. Patients with Barakat syndrome show greater variation in the symptoms and severity.¹

Symptoms and clinical manifestation

The chance of occurrence of the symptoms increases with age. It is noted that by 50 years the patients may develop the triad of symptoms—hypoparathyroidism, sensorineural deafness, and kidney disease. The major clinical manifestations are:

Hypoparathyroidism

• This occurs in 93% of the patients
• Reduced calcium levels in the blood
• Carpopedal spasm—frequent uncontrolled muscle contractions in hands and feet
• Paraesthesia—Tingling sensation in toes, lips, fingertips
• Muscle weakness
• Coarse hair
• Dry, rough skin
• Fingernails that break easily
• Tetany—involuntary contraction of muscle with painful muscle cramps 
• Hypocalcemic seizures

Sensorineural deafness

• Most consistent symptom
• This occurs in 96% of the patients
• Hearing problems
• Usually affects both ears
• It can be moderate to severe

Kidney diseases

• This occurs in 72% of the patients
• Birth defects in the kidney and urinary tract
• Proteinuria—increased protein in urine
• Hematuria—blood in urine
• Nephrotic syndrome— kidney disorder with a large amount of protein loss in urine
• Chronic kidney diseases

Additional symptoms

• Heart defects by birth
• Facial and eye abnormalities
• Psoriasis
• Growth failure
• Diminished intellectual and decision-making capabilities^1,2,3

Diagnosis

Medical history and physical examination play an important role in the diagnosis of the disease. The patient’s blood tests may reveal low serum calcium levels with hyperphosphataemia, hypomagnesaemia, low parathyroid hormone levels, hypercalciuria, and low vitamin D levels. Audiometry can be done to assess hearing loss and a renal function test and renal ultrasonography for kidney function. Genetic analysis helps in the confirmation of Barkat’s syndrome, showing mutations in the GATA3 gene.¹

Prognosis of Barakat syndrome

The rare combination of hypoparathyroidism, sensorineural deafness, and kidney diseases with a family history can help in the diagnosis of Barakat syndrome. Once the disease is diagnosed, a regular checkup of serum calcium and phosphate levels is essential to prevent further complications. 

Factors influencing prognosis

Early diagnosis and treatment play a crucial role in the prognosis of the disease. Deferring the treatment of hypoparathyroidism can cause severe bone diseases like osteoporosis and 

fractures. Kidney diseases like Nephrotic syndrome can be life-threatening if not diagnosed early. Patients with Barakat syndrome also show reduced magnesium and increased phosphorous levels in severe kidney problems, which can complicate the disease. Sensorineural deafness progresses over the years and can affect both ears.² Early diagnosis is also crucial to prevent episodes of seizures due to hypocalcemia.³ The severity of the associated conditions often influences the outcome of the treatment.

Typical progression

Many patients are diagnosed with sensorineural deafness in infancy. It is the most consistent feature, from mild to severe.³ Patients with Barakat syndrome may not show a full spectrum of hypoparathyroidism, hearing loss, and kidney disease in some cases. It may develop at a later stage of life and may progress in due course. Most of the patients report the hearing loss to worsen with age. The symptoms present at the time of diagnosis are highly variable.⁴

Some patients with Barakat syndrome may progress to chronic kidney diseases and may require kidney transplantation. Some younger patients may have kidney cyst progression also. The prognosis of the disease can be dependent on the severity of kidney disease. Some patients may develop insulin-dependent diabetes mellitus in progression. Hypocalcemia can result in brain damage and cause seizures.³

About 0.6% of the patients report isolated hearing loss. In such patients, hypothyroidism and kidney disease may occur at a later stage in their life and hence require continued monitoring.⁴

Long-term outcomes

Quality of life

The key strategy in the management of Barakat syndrome is improving the quality of life of the patients. The disease could impact the daily activities and long-term independence of the patients. It is important to understand the molecular basis of the disease through a genetic analysis. Regular kidney function tests and ultrasounds can help to monitor the progression of any kidney disease. The use of hearing aids, calcium replacement therapy, and other symptomatic treatments can significantly improve the quality of life of the patients.

Medical care

Appropriate genetic counseling should be given to the patients and families about the cause of the disease and in planning subsequent pregnancies. Management of the disease is majorly symptomatic. Hypocalcemia should be closely monitored to prevent potential hypocalcemic seizures. The management of hearing loss typically involves hearing aids and, in some cases cochlear implantation. Management of kidney diseases depends on their severity. Chronic kidney diseases should be diagnosed as early as possible to prevent the progression of end-stage kidney disease. In patients with end-stage kidney disease, kidney transplantation can be done successfully. Patients with minimum complications and minor symptoms have a normal life expectancy.⁴

Importance of early diagnosis, continuous monitoring and treatment

Continuous monitoring and treatment are essential to avoid further complications and to improve the general well-being of the patient. Early recognition of the disease is not only important for genetic counseling but also for a more precise prognosis and to avoid hypocalcemic seizures and hyperphosphatemia complications.⁵

Summary 

Barakat syndrome is a rare genetic disease that shows characteristic symptoms like hypoparathyroidism, sensorineural deafness, and kidney diseases. It occurs due to a mutation in the GATA3 gene. Medical history and genetic analysis play a crucial role in the diagnosis of the disease. Early diagnosis and treatment play a critical role in the prognosis of Barakat syndrome. Management is majorly symptomatic, and the prognosis depends on the severity of the symptoms. Patients with Barakat syndrome may not present with all the symptoms at the time of diagnosis, and the classic triad of symptoms may appear later in life.⁶ The patients generally have good prognoses and a normal life expectancy if there are fewer complications with minor symptoms.