Introduction

A rare genetic disorder, Bachmann-Bupp Syndrome (BABS) was first identified in 2018, with less than 30 known diagnoses worldwide.^1,2 Involving multiple systems throughout the body, BABS is characterised by a large spectrum of symptoms: distinctive alopecia (hair loss), developmental delays, hypotonia (low muscle tone), feeding difficulties, dysmorphic features (atypical physical features), and behavioural abnormalities.³

BABS is a disease that typically becomes evident in early childhood therefore, it is incredibly important that effective and prompt methods are undertaken for its management and treatment. Thus far, treatment methods have primarily focused on alleviating symptoms and enhancing functional abilities, improving the quality of life for not only patients, but their loved ones as well. 

What does Bachmann-Bupp Syndrome look like? 

As with all illnesses, it’s incredibly important to recognise the characteristics BABS may present. While the symptoms of BABS may vary from patient to patient, here are some common symptoms and features of the disease:^1,4-8

• Distinctive alopecia:
  • Absent or spare eyebrows and eyelashes
  • Hair may be present at birth but sparsely and/or of atypical colour
    • If present at birth, hair loss tends to occur in large clumps 
• Hypotonia: low muscle tone
• Hypoglycemia: low blood sugar
• Developmental delays: 
  • Myopathy causes reduced control over muscle and movement. This may present as difficulty walking, climbing stairs, standing from a sitting position, etc.
  • Speech delays
  • Intellectual disability (difficulty learning to read and write) 
• Feeding difficulties
• Hearing loss
• Curved, brittle nails
• Macrocephaly: the baby’s head is significantly larger than normal for their age and sex
• Seizures
• Cysts and lesions in the brain 
• Behavioural concerns and abnormalities
  • For example: anxiety, excessive stubbornness, disruptive behaviour, aggression, poor social skills, ADHD (attention-deficit hyperactivity disorder), autism 
• Other dysmorphic facial features include facial asymmetry, broad foreheads, abnormally large distances between the eyes, elongated face, narrow nose bridge, large earlobes etc. 

Causes of Bachmann-Bupp Syndrome

With parental consent, blood samples were withdrawn from the first identified patient affected by BABS in 2016. These samples were then taken to test for enzyme activity levels of the enzyme ODC (ornithine decarboxylase) and polyamine activity, as well as for genetic testing – DNA sequencing.¹ These tests found that the patient carried a mutation in the gene encoding ODC enzyme, ODC1, and found increased levels of ODC and polyamine. Later studies involving more patients with a confirmed diagnosis and also studies involving mouse models would support these findings.^4-8

BABS is caused by mutations in the ODC1 gene. These mutations are inherited (passed from parent to offspring) in an autosomal dominant pattern, meaning that only one copy of the mutated pathogenic gene needs to be present in order for an individual to develop the disease.⁴ The enzyme ODC catalyses the biosynthesis of polyamines, which play significant roles in cell proliferation (cell growth), gene expression and regulation, transcription and translation, immune responses, and more.⁹ 

While the exact mutation varies between patients, all variants found in patients caused elevated levels of polyamines and ODC. The variation means that the exact mechanisms and pathways affected by the mutation may vary among patients, hence the diverse range of symptoms. 

Management and treatment of Bachmann-Bupp Syndrome

The vast diversity in the symptoms of BABS warrants a need for a multidisciplinary approach to managing the disease, and as such, this often involves a variety of clinicians specialising in different fields: neurologists, geneticists, physical therapists, and occupational therapists. Given the rarity of the disease and its recent discovery, there is yet to be an established disease-modifying therapeutic method today. Much of the treatment of the BABS is targeted towards alleviating the manifestations of the disease.

Supportive treatment of Bachmann-Bupp

• Feeding difficulties: feeding occupational therapy (involves expanding the types and volumes of foods, reducing avoidance behaviour while eating, teaching self-feeding skills), gastronomy tube may also be necessary in severe cases
• Hearing loss: standard treatment according to specialists depending on the severity. This may involve hearing aids, learning sign language and lip reading, etc. 
• Motor dysfunction: physical therapy is used to help maximise patients’ mobility and reduce risk of complications like scoliosis. Use of equipment such as wheelchairs, walkers, etc may also be needed
• Consultation by a psychiatrist and appropriate intervention help guiding the patient and their loved ones through managing and addressing any behavioural concerns
• Seizures: standard treatment according to clinicians, which may involve antiepileptic drugs^2,3,5

Oral treatment with inhibitor DFMO

Difluoromethylornithine (DFMO) is an inhibitor of the ODC enzyme, and is an approved treatment method of West African sleeping sickness (Trypanosomic encephalitis) and neuroblastoma in children. DFMO treatment has been shown to improve alopecia in BABS patients, as well as allowing improvements in muscle tone and development. While this treatment has yet to be approved in the treatment of BABS and is still under investigation, patient clinical trials have shown promise.^2,4,6

Summary

A rare and complex neurodevelopmental disorder, Bachmann-Bupp Syndrome (BABS) presents many challenges in management and treatment as well as diagnosis, given the diversity of its symptoms, from distinctive alopecia and developmental delays to motor dysfunction and behavioural changes. Effective management of the disease requires a multidisciplinary approach, with currently used treatment methods primarily focusing on alleviating symptoms and improving the quality of life for patients. While there is yet to be an established cure for BABS, continued research and clinical trials are progressing and deepening our understanding of the disease, and hold hope for developing targeted disease-modifying therapeutic methods for those affected by BABS, both for the patients and for their loved ones.