diphthamide deficiency syndrome

Diphthamide deficiency syndrome, also known as DPH1 syndrome or Loucks-Innes syndrome, is a rare genetic disorder characterized by several distinct features.

Key symptoms:

• Global developmental delay
• Short stature
• Dysmorphic craniofacial features (abnormal facial structure)
• Sparse hair

These symptoms are often present from birth and can vary in severity among affected individuals. The condition is inherited in an autosomal-recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the syndrome.

Other associated features:

• Macrocephaly (an abnormally large head size)
• Congenital heart disease
• Ectodermal anomalies (abnormalities in the skin, hair, and nails)

It's worth noting that diphthamide deficiency syndrome is a rare condition, and more research is needed to fully understand its causes and effects on affected individuals.

References:

[4] Diphthamide deficiency syndrome is a rare genetic disorder characterized by craniofacial dysmorphism, short stature, ectodermal anomalies, developmental delay, ... [8] An inherited metabolic disorder characterized by global developmental delay, short stature, dysmorphic craniofacial features, and sparse hair that ... [6] Synonyms: DEDSSH1; developmental delay with short stature, dysmorphic facial features, and sparse hair 1; DPH1 syndrome; Loucks-Innes syndrome ; Alt IDs: OMIM: ...

Diphthamide deficiency syndrome, also known as autosomal-recessive diphthamide deficiency syndrome, presents with a range of symptoms that can vary in severity.

Common symptoms include:

• Intellectual disability [2]
• Developmental abnormalities [2]
• Seizures [2]
• Macrocephaly (

Diphthamide deficiency syndrome, also known as DEDSSH1 syndrome, is a rare genetic disorder that affects the translation process in cells. The diagnosis of this syndrome involves several tests to confirm the presence of mutations in the DPH1 gene.

• Whole-exome sequencing: This test is used to identify genetic variants in patients with symptoms consistent with diphthamide deficiency syndrome (DDS). It involves analyzing the entire genome for mutations, including those in the DPH1 gene. [3][5]
• Functional studies and biochemical tests: These tests are used to confirm the pathogenicity of DPH5 variants associated with DDS. They involve studying the effects of these variants on protein function and cellular processes. [6]
• Genetic testing: This test is used to identify mutations in the DPH1 gene, which is responsible for diphthamide deficiency syndrome. It involves analyzing DNA samples from patients to detect genetic variants that may be associated with the disorder. [4]

It's worth noting that a diagnosis of DDS typically requires a combination of clinical evaluation, family history, and genetic testing.

References: [3] by K Ütkür · 2023 · Cited by 6 — The diagnosis of diphthamide deficiency syndrome is based upon whole-exome sequencing of patients with the above-described manifestations that identify ... [4] Genetic tests related with Diphthamide Deficiency Syndrome ; 2 ... [5] by SP Shankar · 2022 · Cited by 10 — We present evidence to prove pathogenicity of the DPH5 variants using functional studies, biochemical tests, and computational modeling and propose that "DPH5- ... [6] by R Schaffrath · Cited by 4 — Diphthamide, a complex modification on eukaryotic translation elongation factor 2 (eEF2), assures reading-frame fidelity during translation.

Diphthamide deficiency syndrome is a rare genetic disorder characterized by the absence or reduced levels of diphthamide, a complex modification on eukaryotic translation elongation factor 2 (eEF2). This modification is essential for reading-frame fidelity during translation.

According to research [4][5], there is no specific drug treatment available for diphthamide deficiency syndrome. However, studies have shown that the absence of diphthamide can lead to sensitivity towards transitional stress induced by hygromycin treatment [3].

It's worth noting that some researchers are exploring the potential therapeutic applications of diphthamide in other contexts, such as cancer treatment [6]. However, these findings are still in the early stages and require further investigation.

In terms of drug treatment, it appears that there is no specific medication available for addressing the underlying deficiency of diphthamide. Instead, researchers may focus on developing strategies to mitigate the effects of diphthamide deficiency or exploring alternative therapeutic approaches.

References:

• [4] R Schaffrath · Cited by 4 — Diphthamide, a complex modification on eukaryotic translation elongation factor 2 (eEF2), assures reading-frame fidelity during translation.
• [5] R Schaffrath · 2023 · Cited by 4 — Diphthamide, a complex modification on eukaryotic translation elongation factor 2 (eEF2), assures reading-frame fidelity during translation.
• [3] by H Hawer · 2020 · Cited by 29 — In contrast, loss of diphthamide induces sensitivity toward transitional stress induced by hygromycin treatment [6].
• [6] by Y Shi · 2024 — We found that diphthamide deficiency promotes the association of eEF2 with p53, leading to enhanced binding of p53 to p21 promoter to induce the expression of ...

Understanding Diphthamide Deficiency Syndrome

Diphthamide deficiency syndrome, also known as diphthamide-deficiency syndrome or DDS, is a rare autosomal-recessive disease that severely affects child development. The symptoms of this condition are diverse and can include intellectual disability, short stature, craniofacial and additional morphological features, hand/foot anomalies, and other clinical symptoms.

Differential Diagnosis

When considering the differential diagnosis for diphthamide deficiency syndrome, it is essential to rule out other conditions that may present with similar symptoms. Some of these conditions include:

• DPH1 knockout (KO): A genetic condition characterized by a deficiency in diphthamide biosynthesis gene 1 (DPH1), which can lead to phenotypes similar to those observed in DDS.
• DPH3 mutations: Mutations in the DPH3 gene, associated with cancer and other conditions, can also cause DDS-like symptoms.
• Other ribosomopathies: Certain types of ribosomopathies, such as those caused by deficiencies in diphthamide synthesis enzymes (DPH1 and DPH3), can present with similar symptoms to DDS.

Key Features for Differential Diagnosis

To accurately diagnose diphthamide deficiency syndrome, clinicians should look out for the following key features:

• Intellectual disability: A significant impairment in cognitive function is a hallmark of DDS.
• Short stature: Individuals with DDS often exhibit short stature and growth delays.
• Craniofacial abnormalities: Dysmorphic craniofacial features are common in DDS patients.
• Hand/foot anomalies: Congenital hand and foot malformations can also be present.

References

1. Hawer, H. et al. (2020) - Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy [2].
2. Shankar, S. P. et al. (2022) - We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of DDS [9].
3. Hawer, H. (2020) - Important anomalies include macrocephaly, developmental delays, short stature, dysmorphic craniofacial features, and congenital heart disease [9].

By considering these key features and differential diagnoses, clinicians can accurately diagnose diphthamide deficiency syndrome and provide appropriate treatment and management for affected individuals.