Lipid storage myopathy with clinical markers of Marfan syndrome: A rare association
A 19-year-old boy, first born to second-degree consanguineous parentage, presented with fatigue, myalgia, pains and aches in the extremities, especially after sustained exercise, muscle cramps and progressive weakness of the proximal lower limbs of 2 years duration, which was gradually worsening over the past 6 months. He had no history of wasting, twitching of muscles, hypertrophy of muscles, myoglobinuria, fluctuations or diurnal variations. There was no history of respiratory distress, bulbar weakness, cranial nerve disturbances, episodes of encephalopathy or cardiac symptoms. There was no family history of similar illness.\nExamination revealed a young boy of thin and tall build with predominant skeletal markers of Marfan syndrome with arm span of 12 cm more than his height (arm span 182 cm, height 170 cm). He also had myopia, high arched palate, kyphoscoliosis [] and wrist sign positivity [] (tip of the thumb covering the entire fingernail of the fifth finger when wrapped around the contralateral wrist) and moderate pectus excavatum []. He also had striae in skin over the back. He had neck flexor weakness, wasted small muscles of hands with proximal muscle weakness of both lower limbs and generalized areflexia, exaggerated lumbar lordosis and waddling gait. There was no ectopia lentis or cardiac or pulmonary involvement.\nOn evaluation, serum creatinine phosphokinase was mildly elevated (343 IU/L).Tandem mass spectroscopic analysis revealed normal levels of free and acylcarnitine species. Cardiac evaluation with ECG and ECHO were normal. There was no evidence of aortic root dilatation. Thyroid profile and serum lactate were normal. Nerve conduction study was normal. X-ray to rule out protrusio acetabulae and magnetic resonance imaging to look for dural ectasia was not done.\nLeft biceps muscle biopsy was subjected to hematoxilin eosin (HE) [], modified Gomori trichrome (MGT), periodic acid Schiff's (PAS), oil red O and a battery of enzyme histochemical stains (succinic dehydrogenase [SDH], nicotinamide adenine dinucleotide tetrazolium reductase [NADH-Tr], adenosine triphosphotase [ATPase, pH 9.5, 4.6, 4.3] and acid phosphatase). Morphologically, skeletal muscle tissue showed preserved architecture, normal endo and perimysial components and polygonal fibers with mild variation in diameter. Moderate numbers of myofibers in each of the fascicle showed multiple fine vacuoles giving a sieve-like appearance. These fibers were present in between normal-appearing fibers, giving a mosaic pattern. SDH and NADH-Tr revealed these fibers to be intensely stained and red granular (Ragged red) on MGT []. The vacuoles were positive to oil red O and negative to PAS and acid phosphatase. Tiny pieces of skeletal muscle tissue fixed in 3% glutaraldehyde embedded in araldite for electron microscopy showed distortion of filamentous pattern, presence of lipid vacuoles and aggregates of mitochondria of varying sizes with altered mitochondrial cristae [].\nThe patient was started on a low dose of carnitine and Co Q. His muscle pain decreased and his neck and proximal muscle weakness of lower limbs improved over the next 2 months. He fulfilled 5/7 of the systemic score in Ghent criteria of Marfan syndrome, although there was no family history of Marfan syndrome. In view of the lack of genetic analysis and family history, the patient does not fulfil Ghent criteria but the patient does have clinical markers of Marfan syndrome and needs close follow-up as evolution of more organ involvement is age dependent. Neck weakness in LSM is reported in one patient[] and association with skeletal markers of Marfan is not reported in the literature.