儿科学与治疗
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Novel limb-girdle muscular dystrophy with rhabdomyolysis and persistently elevated creatine kinase level

Seyedeh Shima SeyedAsadollah Ezadinia

Objective: Rhabdomyolysis is a serious clinical emergency in which skeletal muscle breaks down rapidly. Underlying disorders e.g. LGMD can cause rhabdomyolysis but are often difficult to diagnose due to their marked diversity and rarity.

We report a case of a novel LGMD with rhabdomyolysis as this is the first of its kind to be found in UAE.

CASE REPORT

13-year-old Emirati male from a consanguineous family (1st cousins), presented to ED with sudden onset of generalized muscle cramping, especially in the abdomen, which led to difficulty breathing. He was treated with IV fluids and oxygen in the ED.

General physical and neurological examination were unremarkable. Power was 5/5 throughout except hip flexion/extension/abduction and knee flexion which were 4+/5, 4/5, 4+/5, and 4+/5 respectively. He was found to have cola-colored urine which improved over few days and high serum CK level (spiked at around 200,000 Units/liter) which plateaued after 2 weeks.

Investigations showed CBC, liver function, renal function tests and serum electrolytes, thyroid function tests, serum cortisol, serum LDH, and serum PTH were normal. ECG and chest X-ray were normal.                                                                                                                        

Background of 10 year history of myalgias, 7 year history of persistent hyperCKemia (never normalized but plateaued at a level of thousands over the years) and two previous episodes of rhabdomyolysis (hospitalized both times, cola-colored urine and elevated serum CK levels which receded over a few days; 1st time - walking leisurely, pain in his legs. 2nd time – jumping, arms and legs became stiff).

Further investigations were done at Latifa Hospital, Children’s Hospital of Philadelphia and National Institutes of Health:

Echocardiography showed trace tricuspid valve regurgitation, mild pulmonic insufficiency and a small patent foramen ovale with left to right shunting is noted by color-flow Doppler.

Muscle ultrasound findings were symmetrical and consisted of a mild increase in granular echogenicity. Anterior thighs - mild involvement limited to vastus lateralis. Posterior thighs - mild involvement of the semitendinosus and semimembranosus muscles. Legs - the gastrocnemii were mildly affected, more pronounced in the lateral than the medial aspects. Arms - mild

 

involvement of the posterior deltoid and triceps, and normal to mild involvement of the biceps brachii. Paraspinals - not involved.

Pulmonary function test: FVC decreased by more than 10% in supine position compared to FVC measured in siting position, suggesting muscle weakness.

Muscle MRI findings - musculature shows diffuse symmetric pattern of mild atrophy and fatty infiltration. Soft tissues show mild diffuse edema in the subcutaneous tissues.

Normal nerve conduction studies.

Needle EMG on vastus medialis and right biceps brachii. There was no active denervation. Both muscles - short duration, low amplitude motor units though early recruitment was more evident in the biceps brachii. Abnormal study suggesting a primary muscle disorder without membrane irritability.

The patient is being followed at Neuromuscular and Neurogenetic Disorder of childhood section at NIH. 

DISCUSSION

他的 LGMD 小组显示出一种不太可能致病的变异，并且在三外显子组的进一步测试中是父系遗传的。外显子组确实揭示了 MLIP 基因中的纯合子（预计将被截短）变体，该基因编码肌肉 LMNA 相互作用蛋白（MLIP），在骨骼肌和平滑肌中高度表达，可能与核纤层蛋白病的间充质表型有关。

最近的研究表明，核纤层蛋白突变降低了核稳定性，增加了核脆性，并扰乱了机械转导信号，阐明了许多核纤层蛋白病中的肌肉特异性缺陷。这或许可以解释我们患者出现的横纹肌溶解症。