Kanzaki disease

Kanzaki Disease: A Rare Lysosomal Storage Disorder

Kanzaki disease, also known as Schindler disease type II, is a rare and milder form of the lysosomal storage disorder that typically appears in adulthood. This condition is caused by a deficiency in the enzyme alpha-N-acetylgalactosaminidase (NAGA), which leads to excessive accumulation of glycoproteins within lysosomes.

Key Features:

• Adult-onset: Kanzaki disease usually manifests in adulthood, unlike the more severe infantile and childhood forms of the disorder.
• Mild cognitive impairment: Affected individuals may experience mild cognitive impairment, although this is not a universal feature.
• Sensorineural hearing loss: Some patients with Kanzaki disease may develop sensorineural hearing loss due to abnormalities in the inner ear.
• Weakness and sensory loss: Problems with the peripheral nerves can cause weakness and loss of sensation in affected individuals.

Phenotypic Variability

Kanzaki disease is a clinically heterogeneous disorder, meaning that its presentation can vary significantly among affected individuals. Some patients may exhibit additional features such as angiokeratoma corporis diffusum (a condition characterized by the presence of multiple angiokeratomas), mild intellectual impairment, lymphedema, cardiomegaly, corneal opacity, and facial coarsening.

Prevalence

Kanzaki disease is an extremely rare disorder, with fewer than 20 cases reported to date. As a result, each new case provides valuable insights into the wide range of presentations associated with this condition.

References:

• [2] - Schindler disease type II, also called Kanzaki disease, is a milder form of the disorder that usually appears in adulthood.
• [5] - Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder with three main phenotypes: type I is an infantile-onset neuroaxonal dystrophy; type II, also known as Kanzaki disease, is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment.
• [12] - Schindler disease is a very rare lysosomal storage disorder with fewer than 20 cases described to date.

Kanzaki Disease (Schindler Disease Type II) Signs and Symptoms

Kanzaki disease, also known as Schindler disease type II, is a milder form of the disorder that usually appears in adulthood. The signs and symptoms of this condition can vary from person to person but often include:

• Developmental delay: Affected individuals may experience delays in reaching developmental milestones, such as sitting, crawling, or walking.
• Seizures: Seizures are a common symptom of Kanzaki disease, which can range from mild to severe.
• Cardiomyopathy: A weakened and enlarged heart (cardiomyopathy) is another characteristic feature of this condition.
• Hepatomegaly: An enlarged liver (hepatomegaly) may also be present in some cases.

In addition to these symptoms, affected individuals may experience other complications, such as:

• Mild intellectual impairment: Some patients have been reported to have mild intellectual impairment, but no neurologic signs.
• Lymphedema: Another patient had lymphedema, which is a condition characterized by swelling of the lymph nodes and surrounding tissues.

It's essential to note that Kanzaki disease can progress over time, leading to more severe symptoms. If you or someone you know is experiencing these symptoms, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References:

• [4] Some patients have been reported to have, in addition to angiokeratoma, mild intellectual impairment, but no neurologic signs.
• [14] Schindler disease type II, also called Kanzaki disease, is a milder form of the disorder that usually appears in adulthood. ... Affected individuals may exhibit signs and symptoms beginning in infancy, including developmental delay, seizures, a weakened and enlarged heart (cardiomyopathy), and an enlarged liver (hepatomegaly).

Kanzaki disease, also known as Schindler disease, can be diagnosed through various tests.

• Urine tests: These are used to detect the presence of certain substances in the urine that are associated with Kanzaki disease. [1]
• Blood tests: Blood tests can help confirm a diagnosis by detecting abnormalities in the levels of certain enzymes or other biomarkers. [2]
• Skin biopsies: Skin biopsies may be performed to examine tissue samples for signs of the disease. [3]
• Genetic testing: Genetics testing, such as PCR (polymerase chain reaction), is considered the gold-standard method for diagnosing Kanzaki disease. This test can identify mutations in the NAGA gene that are associated with the condition. [4][5]

It's worth noting that prenatal testing is also available to diagnose Kanzaki disease before birth, using amniotic fluid or chorionic villi samples. [6]

Current Drug Treatments for Schindler/Kanzaki Disease

Unfortunately, there is no specific therapy for individuals with Schindler disease [1]. However, researchers have identified potential treatment options to stabilize alpha-NAGAL, a key enzyme affected in this disorder.

• Pharmacological Chaperones: Small molecules that can act as "chaperones" to stabilize alpha-NAGAL and potentially treat the disease [6][7][8].
• Garman and other small molecules: These molecules have been proposed as potential drugs for treating Schindler/Kanzaki disease, although more research is needed to confirm their efficacy [6][7].

It's essential to note that these treatment options are still in the experimental stages, and further research is necessary to develop effective therapies for this rare disorder.

References:

[1] Context 1 [6] Context 6 [7] Context 6 [8] Context 8

The differential diagnosis of Kanzaki disease, also known as Schindler disease, involves a range of conditions that can present with similar symptoms.

Conditions to Consider

• Duchenne muscular dystrophy
• Limb girdle dystrophy
• Polymyositis
• Other lysosomal storage disorders, such as free sialic acid storage disorders (FSASDs)

These conditions can all present with a range of clinical neurological/neuromuscular deficits due to the accumulation of substrates possessing α-N-acetylgalactosaminidase activity [5][9]. In addition, Kanzaki disease has been associated with atypical features, including a wide range of clinical neurological/neuromuscular deficits [5].

Differential Diagnosis Considerations

• The differential diagnosis includes conditions that can present with similar symptoms to Kanzaki disease, such as Duchenne muscular dystrophy and limb girdle dystrophy.
• Other lysosomal storage disorders, such as FSASDs, should also be considered in the differential diagnosis of Kanzaki disease.
• The clinical diagnosis of Kanzaki patients requires constant monitoring of disease symptoms due to its heterogenous clinicopathology [10].

References

[1] Two major forms of Schindler disease exist – a severe form with onset in infancy (type I) and a milder form with onset in adulthood (type II). Some researchers ...

[2] Kanzaki/Schindler disease is an autosomal recessive disorder caused by the deficient activity of α-N-acetylgalactosaminidase, a lysosome enzyme previously known ...

[3] by T Kanzaki · 1998 — Diagnosis, Differential; Hexosaminidases / deficiency; Hexosaminidases / genetics; Humans; Lysosomal Storage Diseases / diagnosis; Lysosomal Storage Diseases ...

[4] Feb 24, 2023 — The differential diagnosis includes Duchenne muscular dystrophy, dystrophy of the limb girdle dystrophy, and polymyositis. Management.

[5] Symptoms of Schindler/Kanzaki disease include a wide range of clinical neurological/neuromuscular deficits due to the accumulation of substrates possessing ...

[6] Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder with atypical features. It is clinically heterogeneous with 3 main ...

[7] by D Adams · 2020 · Cited by 29 — Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid.

[8] Structural and immunocytochemical studies suggest that a prototype of α-NAGA deficiency in Kanzaki disease and factors other than the defect of α -NAGA may ...

[9] Symptoms of Schindler/Kanzaki disease include a wide range of clinical neurological/neuromuscular deficits due to the accumulation of substrates possessing α-N-acetylgalactosaminidase activity [5][9].

[10] A gradual regression was observed in the CA aneurysm on echocardiography after 1 month. Discussion. According to literature, elevated serum transaminases or gamma glutamyl transpeptidase is observed in 40–60% KD patients [].The majority of the patients show only a mild increase in transaminases, which is < 2-fold of the upper limit of normal, and only a few patients showed 10-fold of the ...