Title
An Unprecedented Case of Early-Onset Duchenne Muscular Dystrophy in a 2-Year-
8-Month-Old Male Child in Pakistan
Abstract:
Most often occurring between the age of three and five, Duchenne Muscular
Dystrophy(DMD) is an X-linked neuromuscular disease that is slowly progressive in
nature. In most cases the onset is not before the age of three, especially where
resources are limited. We present a diagnosis of DMD in a Pakistani male child who
was 2 years and 8 months old. The child had a history of recurrent episodes of
vomiting beginning at three months of age and continuing until the age of one year.
The diagnosis was confirmed by genetic test (MLPA) and high serum creatine
kinase. For very young children, this case highlights the significance of early
diagnosis and detection, especially in countries where there is poor diagnostic
capacity.
INTRODUCTION:
Progressive degeneration of skeletal and cardiac muscle is a characteristic finding in
Duchenne Muscular Dystrophy, an X-linked recessive neuromuscular disorder. Loss
of the dystrophin protein, which is critical for maintaining muscle cell integrity, is due
to mutations of the dystrophin gene. About 1 in 3,500 to 5,000 male live births
globally have DMD. The clinical and genetic profile of DMD is evolving in Pakistan.
The most common mutation among 60 genetically confirmed DMD cases was the
loss of a dystrophin gene exons 45-52, found in a study conducted at the University
of Child Health Sciences and Children’s Hospital Lahore. Regional genetic
heterogeneity was demonstrated by another study in Balochistan, which identified a
patient with a mutation in exon 3. DMD is challenging to diagnose in early stages,
particularly in low-resource settings such as Pakistan where access to genetic
testing and specialized treatment is limited. The absence of newborn screening
programs makes early diagnosis even more challenging. The importance of
heightened clinical suspicion and early genetic assessment in young children has
been revealed through this case study by reporting an unsuspected diagnosis of
DMD in a 2 years, 8months boy child in Pakistan.
CASE PRESENTATION:
We report a 2 year and 8 months old child who was brought to a tertiary care
center. He had a history of intermittent vomiting spells that began when he was three
months old and lasted until he was one year old. He was born to a consanguineous
parents at 41 weeks and 3 days of gestation following an uncomplicated
spontaneous vaginal delivery. His developmental milestones were attained
appropriate for his age. His abdominal issues led to the first laboratory workup,
which was mostly unremarkable except for persistently elevated levels of alanine
aminotransferase (ALY) of 270 U/L to 301 U/L, with a highest of 611 U/L in April
2025. Clinical assessment revealed no issues in spite of the elevation of liver
enzymes. Other tests were conducted, such as metabolic screening, viral hepatitis
serology, and autoimmune liver panels. The hepatitis panel had positive IgG
antibodies for hepatitis A, which suggests previous exposure. Abdominal
ultrasonography and abdominal and pelvic contrast-enhanced CT scans were some
of the imaging studies that revealed mild splenomegaly. Liver fibroscan and MRCP
showed no abnormalities. A neuromuscular etiology was suspected based on the
persistently raised ALT levels in the context of a negative liver-centered evaluation.
Muscle enzymes, including creatine kinase (CK) of 33,846 U/L, lactate
dehydrogenase (LDH) of 1,532 U/L, and aldolase of 102.4 U/L, were found to be
markedly elevated on follow-up studies. Subsequently in the progress of the disease,
physical examination indicated that the child had bilateral calf hypertrophy and a
positive Gower’s sign. Nerve conduction studies established the presence of a
myopathic process. Duchenne Muscular Dystrophy (DMD) was established by
genetic analysis with multiplex ligation-dependent probe amplification (MLPA), which
showed a hemizygous deletion of exon 45 of the dystrophin gene. Interestingly, in
this case, there was no muscular dystrophy family history.
DISCUSSION:
An underdiagnosed but life-threatening X-linked recessive neuromuscular disorder,
Duchenne Muscular Dystrophy (DMD) is often neglected in under-sourced
healthcare systems, such as in Pakistan. Muscle degeneration is the characteristic
finding in DMD, which typically leads to premature death and loss of ambulation.
Early diagnosis is still challenging despite its severity in resourced constrained
environments, where access to genetic diagnosis and specialized treatment is
limited. Our case illustrates the necessity of broadening the diagnostic horizon and
incorporating cheap, early biochemical markers while evaluating chronic elevation of
liver enzymes in young male subjects. The rare early presentation of Duchenne
Muscular Dystrophy in our case where the patient initially presented with elevated
liver enzymes (ALT) and projectile vomiting, symptoms more commonly seen with
liver pathology. But as the literature suggests, skeletal muscle degeneration, a
characteristic of muscular dystrophies, can lead to elevated levels of these enzymes.
Globally, studies like those of Kansu et al. (2023) emphasize the need to screen
children,particularly boys, for neuromuscular diseases like DMD in the event of
conflicting liver tests. The concept that such markers may reflect muscle, rather than
liver pathology was further advanced by Singh et al. (2008), who demonstrated an
association between ALT and creatine kinase (CK) levels in DMD. Although less
often spoken of Dhaliwal et al. (2019) have demonstrated smooth muscle
involvement in severe DMD has been associated with gastrointestinal complications.
Although the patient’s early vomiting episodes ceased, they could have been an
initial symptom of acquiring muscle dysfunction. MLPA gene testing, which
confirmed a deletion in exon 45 of the dystrophin gene, confirmed the diagnosis in
this case. So far , this is consistent with todays best practices globally, where
accurate and early diagnosis relies on genetic testing.
CONCLUSION:
In conclusion, this case emphasizes the necessity for doctors, both domestically
and internationally, to take DMD into account when treating young male patients who
have increased liver enzymes that cannot be explained, particularly when liver
imaging and serology are not involved. Optimizing management and family
counselling requires early detection, which is aided by genetic testing and directed
by high CK levels. Moreover, the intersection of consanguinity and genetic disease
risk in populations such as Pakistan warrants urgent attention through educational
initiatives and healthcare policy support.
References:
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