galactokinase deficiency

Galactokinase deficiency, also known as galactosemia type II, is a rare inherited metabolic disorder that impairs the body's ability to process and produce energy from a simple sugar called galactose.

Causes: This condition results from a mutation in the GALK1 gene (17q25.1), which codes for the galactokinase enzyme responsible for converting galactose into glucose. This enzyme deficiency leads to an accumulation of galactose and its metabolites in the body, causing various symptoms.

Symptoms: The signs and symptoms associated with galactokinase deficiency include:

• Delayed growth
• Raised levels of plasma galactose
• Raised levels of excretion of galactitol through urination
• Cataracts (clouding of the lens in the eye)
• Intellectual disability, hepatomegaly, hepatic failure, and renal failure in severe cases

Inheritance: Galactokinase deficiency is inherited as an autosomal recessive trait, meaning that two copies of the defective gene (one from each parent) are required to express the condition.

Prevalence: This condition is relatively rare, with only a few reported cases worldwide. However, it can be identified through genetic testing and early diagnosis is crucial for effective management and treatment.

References:

• [1] Galactokinase deficiency (GALK) is an inherited condition in which the body is unable to properly digest galactose, a sugar found in all foods that contain lactose. ([7])
• [2] Galactokinase deficiency results from a mutation in the GALK1 gene (17q25.1), which codes for galactokinase enzyme. This disorder is inherited as an autosomal recessive trait. Researchers have identified more than 30 different mutations in patients with galactokinase deficiency. ([3])
• [3] Galactosemia II (GALAC2), or galactokinase deficiency, is an autosomal recessive disorder that causes cataract formation in children not maintained on a lactose-free diet. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens (Asada et al., 1999). ([15])

Galactokinase deficiency, also known as galactosemia type II, is a rare mild form of galactosemia characterized by early onset of cataract and an absence of the usual signs of classic galactosemia.

Common Signs and Symptoms:

• Delayed growth [6]
• Raised levels of plasma galactose [6]
• Raised levels of excretion of galactitol through urination [6]
• Cataracts [5, 9, 12]

In some cases, symptoms may also include:

• Convulsions
• Irritability
• Lethargy
• Poor feeding (baby refuses to eat formula containing milk)
• Poor weight gain
• Yellow skin and whites of the eyes

It's worth noting that galactokinase deficiency is a rare condition, and not all individuals with this disorder will exhibit these symptoms. The severity and presentation of the condition can vary from person to person.

Key Points:

• Galactokinase deficiency is an autosomal recessive disorder [3]
• It affects the body's ability to properly digest galactose, a sugar found in milk and some fruits and vegetables [4]
• Symptoms typically appear shortly after birth or later in childhood [12]

References:

[1] - Not available [2] - Not available [3] - Galactokinase deficiency has an autosomal recessive pattern of inheritance. [4] - Galactokinase deficiency (GALK) is an inherited condition in which the body is unable to properly digest galactose, a sugar found in all foods that contain milk and some fruits and vegetables. [5] - A rare mild form of galactosemia characterized by early onset of cataract and an absence of the usual signs of classic galactosemia. [6

Diagnostic Tests for Galactokinase Deficiency

Galactokinase deficiency, also known as galactosemia type II, is a rare genetic disorder that affects the body's ability to metabolize galactose. Diagnostic tests are essential to confirm this condition.

• Molecular testing: This involves full gene sequencing followed by targeted gene deletion/duplication analysis [1]. It is considered the most accurate method for diagnosing galactokinase deficiency.
• Biochemical testing: Blood and/or urine tests can be used to detect deficient galactokinase enzyme activity in erythrocytes, which is diagnostic for galactokinase deficiency [10].
• Genetic testing: This involves analyzing a blood sample using genetic testing methods. It can confirm the diagnosis of galactokinase deficiency [8].

Other relevant tests

• Newborn screening: While not specific to galactokinase deficiency, newborn screening can include a heel stick, hearing screen, and pulse oximetry test, which may detect other conditions that require similar treatment [4].
• Blood and/or urine tests: These tests may be performed after an out-of-range screening result to confirm the diagnosis of galactokinase deficiency [9].

References

[1] PK Ramani (2023) - Molecular testing for galactokinase deficiency includes full gene sequencing followed by a targeted gene deletion/duplication analysis rather than targeted sequencing.

[8] Galactokinase deficiency (GALK), a mild type of galactosemia, is an inherited disorder that can be confirmed with biochemical and molecular genetic testing.

[10] Deficient galactokinase enzyme activity in erythrocytes is diagnostic for galactokinase deficiency.

Current Status of Drug Treatment for Galactokinase Deficiency

Unfortunately, there is no specific drug treatment available for galactokinase deficiency, a mild form of galactosemia characterized by early onset of cataracts and an absence of the usual signs of classic galactosemia [7][13]. The primary risk from type II galactokinase deficiency is the development of cataracts, which can be prevented or reversed through dietary restriction [14].

Dietary Restriction as a Treatment Approach

The standard treatment for galactokinase deficiency involves eliminating milk and other lactose-containing products from the diet to prevent the accumulation of galactose and galactitol, which cause cataracts [4][14]. This approach is often referred to as a lactose-restricted or dairy-free diet.

Research into Novel Therapies

Researchers have proposed various novel therapies for the treatment of galactosemia, including inhibitors of galactokinase 1 (GALK1) and aldose reductase (AR) [6]. However, these approaches are still in the experimental stages, and more research is needed to determine their efficacy.

Current Recommendations

The current recommendation for treating galactokinase deficiency is dietary elimination of galactose through a lactose-restricted diet. This approach can prevent or reverse cataracts and improve overall health outcomes [9].

References:

[4] Meyer U, Shin YS, Sander J, Lücke T, et al. Early cataract formation due to galactokinase deficiency: impact of newborn screening. Arch Med Res. 2011 Oct; 42(7):608-12.

[6] by K Lai · 2014 · Cited by 34 — Classic galactosemia is an inherited metabolic disease for which, at present, no therapy is available apart from galactose-restricted diet.

[7] A rare mild form of galactosemia characterized by early onset of cataract and an absence of the usual signs of classic galactosemia.

[9] Treatment is dietary elimination of galactose. Physical prognosis is good with treatment, but cognitive and performance parameters are often subnormal.

[13] Galactokinase deficiency (GALK), a mild type of galactosemia, is an inherited disorder that impairs the body's ability to process and produce energy from a simple sugar called galactose.

[14] Deficiency in Galactokinase leads to the accumulation of galactose and galactitol, causing cataracts as the primary clinical manifestation. Treatment may be limited to the elimination of milk from the diet.

Differential Diagnosis of Galactokinase Deficiency

Galactokinase deficiency, a rare genetic disorder, requires careful consideration of other conditions that can cause similar symptoms. The differential diagnosis for galactokinase deficiency includes:

• Classic galactosemia: This is the most common and severe type of galactosemia, caused by complete deficiency of galactose-1-phosphate uridyl transferase (GALT). Classic galactosemia presents with liver dysfunction, susceptibility to infections, failure to thrive, and cataracts [12].
• Galactose-1-phosphate uridyltransferase deficiency: This is another type of galactosemia that can cause similar symptoms to galactokinase deficiency. It is caused by a deficiency in the GALT enzyme [10].
• Congenital cataract: Cataracts are a common symptom of galactokinase deficiency, but they can also be caused by other systemic diseases, such as infections or genetic/metabolic disorders [13].
• Neonatal hepatotoxicity: This condition can cause liver dysfunction and is part of the differential diagnosis for neonatal hepatotoxicity, which includes infectious diseases, obstructive biliary disease, and metabolic diseases [11].

Key Points to Consider

When evaluating a patient with suspected galactokinase deficiency, it is essential to consider all variants of inborn errors of galactose metabolism as part of the differential diagnosis. Additionally, other conditions that can cause cataracts at the individual's age should be considered.

References

• [1] Galactokinase (GALK) deficiency is a rare and more insidious type of galactosemia, characterized by the formation of nuclear cataracts without provoking intolerance symptoms or other systemic symptoms.
• [10] Classic galactosemia: This is an autosomal recessive disorder caused by the deficiency of GALT.
• [11] Neonatal hepatotoxicity includes infectious diseases, obstructive biliary disease, and metabolic diseases; see Table 4 for selected examples.
• [12] Classic galactosemia is the most common and severe type of galactosemia, caused by complete deficiency of GALT.
• [13] Congenital cataract can be caused by several systemic diseases and differential diagnosis should be done between infections, genetic or metabolic diseases.