Currently 6-months age male infant, fourth product of consanguineous marriage, delivered normally weighing 2500gms, said to have cried immediately after birth, presented with breathing difficulty at 1-month age.
Since then, the child has had frequent hospitalizations for recurrent respiratory infections. At presentation coughing was marked with high grade fever. Respiratory distress was evident with difficulty in breast feeding. There was suck-rest-suck cycle. Short periods of feeding were interspersed with short periods of being held up against the shoulder providing rest and relief from breathlessness. Profuse sweating also accompanied the feeding efforts. He is immunized for age. He had history suggestive of developmental delay more marked in gross motor and fine motor abilities, whereas language and social milestones were less affected.
Family history is significant. Child is the fourth born of second-degree consanguineous marriage i.e., mother of child is married to her maternal uncle’s son. The couple’s first child i.e., eldest daughter 7-years age is attending primary school, second child daughter expired at 8 months’ age due to recurrent pneumonia, third child son expired at 15 months’ age due to cardiac failure secondary to pneumonia probably cardiomyopathy, fourth is the present propositus.
The anthropometry parameters were as follows: weight(kg) 6.0(< 3rd centile for age), Crown-Heel Length(cms) 62(<3rd centile for age), Occipito-Frontal circumference(cms) 43(median), Mid-Upper-Arm Circumference(cms) 13, Wt./L is -1 SD, undernourished but not Severe Acute Malnutrition. Child was conscious, temperature 101OF, respiratory rate (RR) 60/min, heart rate (HR) 128/min, Non-Invasive Blood Pressure 85/65mmHg, Capillary Refill Time<3 sec, oxygen saturation 86% on room air. Though overt cyanosis was not present desaturation was noted on pulse oximetry which responded to oxygen by hood box at 6L/min. No pallor, icterus, cyanosis, clubbing, significant lymphadenopathy or pedal edema was noted. Mouth distinct with thick lips and protruding thick tongue.
Cardiovascular examination showed HR 128/min i.e., tachycardia with no chest deformity and cardiac apex at left 5th intercostal space lateral to mid clavicular line, heart sounds S1+, S2+ and no murmur. Respiratory system examination showed RR 60/min i.e., tachypnea, chest symmetrical, movements equal, chest expansion appears limited, intercostal and subcostal retraction as evidence of respiratory distress, bilateral air entry present and bilateral fine crepitations heard in all areas. Central Nervous System examination revealed a conscious and oriented child with a symmetrical face during both awake and asleep states. Rooting, sucking, swallowing reflexes were present and well-coordinated with no evidence of cranial nerve palsy. Neurodevelopmental examination in various fields revealed the following: Gross Motor- Supine: symmetrical posture, arms extended at elbows bilaterally, legs extended at knees bilaterally, head lag on pull to sitting position features as evidence of generalized hypotonia, deep tendon reflexes diminished, superficial reflexes present. Prone: legs extended, holds chin up, turns head, unable to support weight on forearm. Ventral suspension: head lifted momentarily to plane of body. Primitive reflexes: Moro’s reflex absent (normal for age), palmar grasp reflex absent (normal for age), plantar grasp reflex present (normal for age), sucking and swallowing coordinated but swallowing slower than before because of respiratory distress and large tongue. Fine motor- Adaptive: although spontaneous hand opening achieved and able to grasp rattle with hand, but unable to transfer object from one hand to other. Language: coos and babbles. Social: smiles to mother, shows likes and dislikes, wide eyed appears excited at sight of food. Neuromotor and developmental examination reveals a floppy infant [Figure 1] which could be due to hypothyroidism or Down’s syndrome or Werdnig-Hoffmann disease or Pompe Disease. Though the child is chronologically 6-months age he has developmental quotient of 3-months. Gastrointestinal Tract examination showed mild diffuse distension of abdomen with an abdomino-thoracic type of respiration, umbilicus normal and no hernia, no obvious scars/sinuses, no prominent superficial vessels, massive hepatomegaly with liver span of 11cm, bowel sounds present.
The complete blood count changes over 10 days revealed hemoglobin decreasing from 13.2gm/dl to 10.9gm/dl, total leukocyte count decreasing from 18,720/mm3 to 11,000/mm3, differential leukocyte count showed following changes (%): Polymorphs 45 to 27, lymphocytes 45 to 58, eosinophil from 10 to 9, monocytes from 0 to 6, platelet count was steady at 308 x103/µl, Liver function tests showed elevated liver enzymes(IU/L) (SGOT: 517(17-59), SGPT: 151(21-72), CPK-MB:62(<25); CPK-NAC:739(55-170); Renal function tests were normal, Thyroid function tests were normal.
Electrocardiography (ECG) shows prominent P waves, short PR interval, large QRS complexes in all leads, left axis deviation which is in contrast to the expected right axis deviation for this age, evidence of biventricular hypertrophy seen. ST depression and T-wave inversion changes seen indicative of hypertrophic cardiomyopathy [Figure 2].
Chest X-ray shows massive cardiomegaly and cardio thoracic ratio >70 % [Figure 3].
Echocardiography revealed concentric left ventricular hypertrophy, left ventricular ejection fraction 60%, lateral wall thickness 8.5mm, inter-ventricular septum 8mm, no left ventricular outflow tract obstruction and trivial mitral regurgitation.
Dried Blood Spot (DBS) Assay confirmed our clinical suspicion for the diagnosis of Pompe Disease: Total acid α-glucosidase(A) 4.84nmol/hr/ml (10-60); Lysosomal acid α-glucosidase(B) 0.19nmol/hr/ml (4.51-15.0); Ratio(B/A) 0.04 (0.3-0.8)
Parents were advised follow-up after 1 month.
Supportive therapy: Propped up, oxygen inhalation, monitoring with pulse oximetry, improved to 94%/120/min. IV Lasix for 3-days, antibiotics administered were Ampicillin-Cloxacillin combination along with Cefotaxime for 9days, followed by Syrup Ampiclox per oral for 5days. Advised immunization with Pneumococcal vaccine along with vaccines in the National Immunization Schedule as well as Rotavirus vaccine. Breast feeding was advised for its numerous benefits along with complementary feeding and multivitamin drops with oral iron therapy. Parents were counselled regarding the need for gentle, graduated physical therapy to strengthen muscles and enable movements which may be beneficial with specific therapy. Follow-up echocardiography showed no change and hemoglobin improved to 11.4gm/dl. Specific therapy: Enzyme replacement therapy (ERT) with recombinant human α-glucosidase (Alglucosidase alfa) is available for treatment of PD which is capable of preventing deterioration or reversing abnormal cardiac and skeletal muscle functions. Cost of Myozyme (Alglucosidase alfa) is limiting due to resource crunch and hence funding is being pursued. Parents are keen for follow-up with ERT together with suggested physical and supportive therapy.